WO2017211947A1 - Chemosensitivity predictive biomarkers - Google Patents
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- WO2017211947A1 WO2017211947A1 PCT/EP2017/063952 EP2017063952W WO2017211947A1 WO 2017211947 A1 WO2017211947 A1 WO 2017211947A1 EP 2017063952 W EP2017063952 W EP 2017063952W WO 2017211947 A1 WO2017211947 A1 WO 2017211947A1
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Abstract
The present invention provides a method for predicting the response of a subject having small cell lung cancer (SCLC) to chemotherapy, the method comprising: determining the copy number aberration (CNA) status of at least 10 genomic segments, defined herein, of a circulating tumour cell (CTC) sample obtained from the subject, thereby obtaining a sample CNA profile; and analysing said sample CNA profile to classify the sample as being chemosensitive or chemorefractory. Also provided are related methods for stratifying a population of subjects according to SCLC chemosensitivity, and systems for carrying out the methods of the invention.
Description
CHEMOSENSITIVITY PREDICTIVE BIOMARKERS
Field of the invention
The present invention relates to methods of assessing and
classifying tumour characteristics, including tumour chemosensitive or chemorefractory status, based on molecular markers, particularly copy number aberrations (CNAs), and to kits and related products for use in such methods.
Background to the invention
Small-cell lung cancer (SCLC) , an aggressive neuroendocrine tumour with early dissemination and dismal prognosis, accounts for 15-20% of lung cancer cases and -200,000 deaths each year. Most cases are inoperable, and biopsies to investigate SCLC biology are rarely obtainable. Minimally invasive monitoring of patients with
SCLC is sorely needed to optimise therapy selection. Due to the rarity of resections and difficulties associated with the collection of tissue biopsies the genomic landscape of SCLC is less well studied than many other human cancers, with less than 200 tumours reported on to date. However, three recent landmark studies (2,3,4) revealed high levels of genetic alterations with a mutation
frequency second only to melanoma (5) . SCLC is defined by allelic loss of both RBI and TP53 and mutations in the remaining alleles. In addition, amplification of BCL-2, Myc genes and S0X2 are common, together with mutations in NOTCH family genes and an expansive range of less frequent alterations (6) . Despite recent progress, there is no molecular data linking specific genetic aberrations with
subsequent clinical outcomes.
Previously, we and others have demonstrated the prevalence of CTCs in SCLC (7), that the number of CTCs are a prognostic factor for progression free survival (PFS) and overall survival (OS) (8,9), and that SCLC CTCs are tumorigenic in immune compromised mice forming patient CTC Derived eXplants (CDX, 1) . Preliminary observations of CTCs and CDX suggest differences in CNA between chemosensitive and chemorefractory disease (1) . Moreover, common regions of both
gain (3q, 5p) and loss (3p, 13q, 17p) across SCLC patients have been reported (5, 6, 7) .
There remains an unmet need for biomarkers, especially minimally invasive biomarkers, that could predict at baseline whether a patient will be chemosensitive or chemorefractory . The present invention addresses these and other needs.
Brief Description of the Invention
Broadly, the present inventors have found that a signature of 16 CNA segments stratifies CTC samples from chemosensitive and
chemorefractory SCLC patients. Significantly, the 16 CNA segments described herein were found to classify CTC samples as
chemosensitive or chemorefractory with a very high level of
predictive performance. By contrast, analysis of 13 genes that have previously been reported (5, 6) to be frequently amplified or deleted in SCLC, found that although there was heterogeneity amongst the 13 gene signature, there was no obvious clustering of pre- treatment samples form chemosensitive patients separately from chemorefractory patients (see Figure IB) . This comparative result evidences the breakthrough nature of the invention presently described .
Accordingly, in a first aspect the present invention provides method for predicting the response of a subject having small cell lung cancer (SCLC) to chemotherapy, the method comprising:
determining the copy number aberration (CNA) status of at least 10, 11, 12, 13, 14, 15 or at least 16 genomic segments of a circulating tumour cell (CTC) sample obtained from the subject, thereby obtaining a sample CNA profile; and
analysing said sample CNA profile to classify the sample as being chemosensitive or chemorefractory,
wherein said at least 10 genomic segments are selected from the group of genomic segments consisting of:
Segment-1: chromosome 16, start: 53467889, end: 87739290;
Segment-2 : chromosome 18, start: 2537524, end: 76762677;
Segment- 3: chromosome 13, start : 21547171, end : 61148012;
Segment- 4 : chromosome 11, start : 77371041, end: 112140678;
Segment- 5: chromosome 4, start: 1873151, end: 187647876;
Segment- 6: chromosome 13, start : 75858808, end : 78338377;
Segment- 7 : chromosome 13, start : 78469616, end: 111567416;
Segment- 8: chromosome 16, start : 71315292, end : 72210777;
Segment- 9: chromosome 10, start : 83635070, end: 131982785;
Segment- 10 chromosome 19, start : 47724081, end 57100279;
Segment- 11 chromosome 5, start : 15500305, end : 44820530;
Segment- 12 chromosome 9, start : 15552895, end : 17503921;
Segment- 13 chromosome 15, start : 25200133, end: 100882210;
Segment- 14 chromosome 21, start : 17102344, end 37860058;
Segment- 15 chromosome 8, start : 71581600, end : 77913280; and
Segment- 16 chromosome 19, start : 20802867, end 23578362,
wherein said start and end positions are according to the numbering system of Genome Reference Consortium GRCh37, patch release
dated 28 June 2013.
In some cases analysing said sample CNA profile comprises applying a computational classifier, such as a machine learning model, to said sample CNA profile, wherein said computational classifier is adapted to assign an unknown CNA profile to the chemosensitive class or the chemorefractory class based on a training set of sample CNA profiles of said at least 10 genomic segments obtained from training samples of known chemosensitive/chemorefractory status, which training samples include at least 2, 3, 4, or at least 5 known chemosensitive SCLC CTC samples and at least 2, 3, 4, or at least 5 known
chemorefractory SCLC CTC samples. The computational classifier may optionally have been subjected to multiple rounds of training in order to tune model parameters and/or optimise performance of the computational classifier on the training samples.
In some cases the computational classifier comprises a machine learning model. In particular, the classifier may comprise a support vector machine (SVM) or a partial least squares (PLS) regression. The SVM may be a radial basis SVM.
In certain cases, the SVM comprises a Gaussian Radial Basis kernel function. In particular, the parameters that support the classifier may be as follows:
parameter : cost C = 0.25
Hyperparameter : sigma = 0.0476184222095904
Number of Support Vectors : 43.
In some cases in accordance with the first aspect of the present invention, analysing said sample CNA profile comprises comparing the sample CNA profile with at least one reference CNA profile of said 10 genomic segments, wherein said at least one reference CNA profile comprises :
(i) a chemosensitive reference CNA profile derived from at least one CTC sample from a chemosensitive SCLC subject; and/or
(ii) a chemorefractory reference CNA profile derived from at least one CTC sample from a chemorefractory SCLC subj ect .
Preferably, the sample CNA profile is compared with both (i) and (ii) . In particular, said sample CNA profile may be compared with both the chemosensitive reference CNA profile and the
chemorefractory reference CNA profile and an assessment of best fit is used to classify the sample as being chemosensitive or
chemorefractory . In some cases, the sample CNA profile is compared with the average copy number values shown in Table 2 in respect of each of said at least 10 genomic segments. When the sample copy number determined for a given genomic segment matches the average copy number for that same segment for the chemosensitive or
chemorefractory class, respectively, as set forth in Table 2, the sample may be predicted to be of that matching class. The more of said genomic segments that are found to match a particular
chemosensitive/chemorefratory class in accordance with Table 2, the more confident can be the prediction of chemosensitive or
chemorefractory status.
In certain cases, the chemosensitive reference CNA profile is an average of at least 5, 6, 7, 8, 9 , or at least 10 CNA profiles each from CTCs of known chemosensitive SCLC subjects.
Likewise, the chemorefractory reference CNA profile may be an average of at least 5, 6, 7, 8, 9, or at least 10 CNA profiles each from CTCs of known chemorefractory SCLC subjects.
In some cases in accordance with the first aspect of the present invention, said at least 10 genomic segments comprise all of the following 16 segments:
Segment-1: chromosome 16, start: 53467889, end: 87739290;
Segment-2 : chromosome 18, start: 2537524, end: 76762677;
Segment-3: chromosome 13, start: 21547171, end: 61148012;
Segment-4: chromosome 11, start: 77371041, end: 112140678;
Segment-5: chromosome 4, start: 1873151, end: 187647876;
Segment-6: chromosome 13, start: 75858808, end: 78338377;
Segment-7: chromosome 13, start: 78469616, end: 111567416;
Segment-8: chromosome 16, start: 71315292, end: 72210777;
Segment-9: chromosome 10, start: 83635070, end: 131982785;
Segment-10: chromosome 19, start: 47724081, end: 57100279;
Segment-11: chromosome 5, start: 15500305, end: 44820530;
Segment-12: chromosome 9, start: 15552895, end: 17503921;
Segment-13: chromosome 15, start: 25200133, end: 100882210;
Segment-14: chromosome 21, start: 17102344, end: 37860058;
Segment-15: chromosome 8, start: 71581600, end: 77913280; and
Segment-16: chromosome 19, start: 20802867, end: 23578362,
wherein said start and end positions are according to the numbering system of Genome Reference Consortium GRCh37, patch release 13, dated 28 June 2013.
In some cases, determining the CNA status of each genomic segment comprises determining the copy number of one or more (e.g. 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) loci within the segment. The present inventors have found that the gene loci within each of said segments are grouped in terms of their genomic locations and copy number changes. Therefore, determining the copy number of a part of a
segment (e.g. a single gene loci or a section of at least 50 base pairs, e.g., at least 1 kilobases in length whether within a single loci or spanning two or more loci) may be used to infer the copy number of the entire segment. In some cases, the genomic segments comprise the following loci, said loci being indicated by Gene ID as set forth in the GeneRIF database as available on 3 February 2014 at the NCBI web site
( ftp : // ftp . ncbi . nlm . nih . gov/gene/GeneRIF/ ) :
(i) segment 1: C16orf80, CSNK2A2, CCDC135, KATNB1, KIFC3, CTD- 260009.1, CNGB1, TEPP, ZNF319, USB1, MMP15, NLRC5, CPNE2, FAM192A, RSPRY1, ARL2BP, PLLP, CCL22, CX3CL1, CCL17, CIAPIN1, COQ9, POLR2C, DOK4, CCDC102A, GPR114, GPR97, CETP, GPR56, NUDT21, OGFOD1, BBS2, MT4, MT3, MT2A, MT1E, AC026461.1, MT1M, MT1A, MT1B, MT1F, MT1G, MT1H, MUX, NUP93, SLC12A3, HERPUD1, CNOT1, AMFR, GNAOl, CES5A, SLC38A7, GOT2, CCDC113, PRSS54, GINS3, NDRG4, SETD6, RP11 -105C20.2 , FTO, LPCAT2, CAPNS2, SLC6A2, CES1, MMP2, IRX3, IRX5, IRX6, RP11- 324D17.1, RPGRIP1L, ZCCHC14, FOXF1 , MTHFSD, FOXC2, FOXL1, C16orf95, JPH3, AC010536.1, FLJ00104, MAP1LC3B, RP11-178L8.4 , FBX031, IRF8, EMC8 , COX4I1, MBTPS1, HSDL1, DNAAF1 , TAF1C, ADAD2, KCNG4 , WFDC1, ATP2C2, KIAA1609, COTL1, KLHL36, USP10, CRISPLD2, ZDHHC7, GINS2, SLC38A8, CDH8, KIAA0513, DYNLRB2 , CDYL2, C16orf74, CMC2 , CENPN, ATMIN, C16orf46, GCSH, PKD1L2, BCMOl, GAN, CMIP, PLCG2 , SDR42E1, HSD17B2, MON1B, SYCE1L, ADAMTS18 , MPHOSPH6, CDH13, HSBP1, MLYCD, NUDT7, VAT1L, NECAB2, RBL2 , AKTIP, OSGIN1, CLEC3A, WWOX, PIH1, MAF, GSE1, RP11-58C22.1, FAM92B, RP11 - 680G10.1 , CNTNAP4, CDH11, AGRP, CDH5, THAP11, NUTF2, EDC4, NRN1L, RLTPR, ACD, PARD6A, ENKD1,
C16orf86, GFOD2, CENPT, RANBP10, TSNAXIP1, CTCF, FAM65A, ATP6V0D1, NAE1, RP11-77K12.1, TMEM17 OA, CHST6, CHST5, ESRP2, PLA2G15, SLC7A6, SLC7A60S, CDH16, PSKH1, CFDP1, RP11- 77K12.7 , CMTM4 , RRAD, CA7, PDP2, NFATC3, DYNC1LI2, FAM96B, CES2, CES3, CES4A, CCDC79, TMEM231, CTRL, CTC-479C5.12, PSMB10, LCAT, SLC12A4, DPEP3, DPEP2, DUS2L, DDX28, GABARAPL2, ADAT1, KARS , RFWD3, MLKL, FA2H, WDR59, ZNRF1, LDHD, ZFP1, CTRB2, CTRB1, BCAR1 , CMTM3 , PRMT7, TERF2IP, CMTM2 , BEAN1, RP11- 403P17.5, AC025287.1, AC132186.1, TK2, CKLF, CKLF-CMTM1, CMTM1, SMPD3, CDH1, TMC07, HAS3, CHTF8, CHTF8, CIRH1A, SNTB2, VPS4A, RP11- 343C2.3, COG8, PDF, RP11-343C2.8 , COG8, RP11-343C2.7, NIP7, TMED6,
TERF2, CYB5B, CDH3, HSD11B2, ZFP90, ZFHX3, C16orf47, ZDHHC1, LRRC36, CBFB, TPPP3, KCTD19, C16orf70, B3GNT9, TRADD, FBXL8, RP11-5A19.5, HSF4 , NOL3, KIAA0895L, EXOC3L1, E2F4, ELM03, LRRC29, AC040160.1, TMEM208, FHOD1, SLC9A5, and PLEKHG4;
(ii) segment 2: APCDD1 , NAPG, PIEZ02, GNAL, CHMP1B, MPPE1, IMPA2, RBBP8, TMEM241, CABLESI , VAPA, RIOK3, NDUFV2, ANKRD12,
IMPACT, SLMOl, HRH4, SPIRE1, C18orf8, AP005482.1, CEP76, PSMG2, PTPN2, SEH1L, CEP192, LDLRAD4, NPC1, TTC39C, CABYR, OSBPL1A, ZNF521, AQP4, LAMA3, GATA6 , KCTD1, SS18, PSMA8, TAF4B, CHST9, FAM210A, RNMT, MC5R, PTPRM, ARHGAP28 , LAMA1 , LRRC30, RP11-865B13.1, AP001094.1, CTAGE1, CTAGE1, TXNDC2, TWSG1, RALBP1, PPP4R1, RAB31, MYL12A,
MYL12B, TGIF1, ANKRD29, RAB12, SOGA2, C18orf42, MYOM1, CDH2,
L3MBTL4, LPIN2, EMILIN2, ZFP161, DSC2, DSC1, DSC3, SMCHD1, EPB41L3, TMEM200C, DLGAP1, SLC14A1, SIGLEC15, EPG5, PSTPIP2, ATP5A1, HAUS1, C18orf25, RNF165, LOXHD1, ST8SIA5, PIAS2, KATNAL2, TCEB3CL2,
TCEB3CL, TCEB3C, TCEB3B, HDHD2, IER3IP1, IER3IP1, SKOR2 , SMAD2, ZBTB7C, AC091150.1, CTIF, SMAD7, SETBP1, SLC14A2, KIAA1328, DYM, DSG1, ACAA2, RP11- 886H22.1 , MY05B, CCDC11, MBD1, CXXC1, SKA1, MIB1, C18orf32, RPL17-Cl 80RF32 , RPL17, LIPG, RP11 -595B24.2 , CELF4 , MAPK4, MRO, ME2 , ELAC1, RP11- 729L2.2 , SMAD4 , MEX3C, SLC25A52, PIK3C3, TPGS2, RIT2, DSG4, DSG3, DSG2, TTR, B4GALT6, SYT4, FHOD3, TRAPPC8, RNF125, RNF138, MEP1B, FAM59A, NOL4, DTNA, MAPRE2, ZNF397, ZSCAN30, ZNF24, ZNF396, RP11-322E11.6, INO80C, GALNT1, C18orf21, RPRD1A, MOCOS, ELP2, SLC39A6, METTL4 , NDC80, KLHL14 , AC012123.1, CCDC178, ASXL3, DCC, RP11-4104.1, RP11- 433A23.1 , SOCS6 , RTTN, ESCOl, SNRPD1, ABHD3, MBD2, POLI, STARD6, C18orf54, DYNAP, RAB27B, CD226, CCDC68,
TCF4, RNF152, PIGN, KIAA1468, TNFRSF11A, ZCCHC2, PHLPP1, AC015989.1, AC015989.2, BCL2, MC4R, SERPINB5, SERPINB12, SERPINB13 , SERPINB4, SERPINB3, SERPINB7, SERPINB2, SERPINBIO, AC009802.1, HMSD, SERPINB8, CDH20, VPS4B, DOK6, DSEL, KDSR, PMAIP1, NARS, ATP8B1, NEDD4L, ALPK2, MALT1, ZNF532, SEC11C, GRP, RAX, CPLX4, LMAN1, CCBE1, TMX3 , TXNL1, CDH19, FECH, CCDC102B, RP11- 861L17.3 , WDR7 , CDH7, BOD1L2, ST8SIA3, ONECUT2, GALR1, CBLN2, RP11-723G8.2 , NETOl, RP11-169F17.1 , RP11- 321M21.3, C18orf62, RP11-94B19.4 , ZNF516, RP11-17M16.1 , RP11- 111H3.1, RP11-162A12.2, ZNF236, MBP, ZADH2 , TSHZ1, ZNF407, FBX015, TIMM21, CYB5A, C18orf63, FAM69C, CNDP2 , CNDP1, and SALL3;
(iii) segment 3: SGCG, SACS, TNFRSF19 , MIPEP, AL139080.1,
C1QTNF9B, SPATA13, C1QTNF9, C1QTNF9B-AS1 , PARP4, ATP12A, RNF17, CENPJ, LSP1, PABPC3, FAM123A, MTMR6, NUPL1, ATP8A2, AL138815.1, AL138815.2, SHISA2, RNF6, CDK8 , WASF3, GPR12, USP12, RPL21, RASL11A, GTF3A, MTIF3, LATS2, SAP18, SKA3 , MRP63, ZDHHC20, ZDHHC20, EFHA1, FGF9, LNX2, POLR1D, GSX1, PDX1, RXFP2 , FRY, ZAR1L, BRCA2 , N4BP2L1, RP11-298P3.4, N4BP2L2, PDS5B, KL, STARD13, RFC3, SLC7A1, PA 3 , ATP5EP2, CDX2, PRHOXNB, FLT3, UBL3, LINC00544, KATNAL1, HMGB1, USPL1, ALOX5AP, MEDAG, TEX26, HSPH1, B3GALTL, FLT1, POMP, SLC46A3, MTUS2, NBEA, DCLK1, MAB21L1, CCNA1 , SOHLH2 , CCDC169-SOHLH2 , CCDC169, SPG20, SPG20OS, SERTM1, DLEU1, RFXAP, FAM124A, SERPINE3, INTS6,
WDFY2, DHRS12, CCDC70, ATP7B, ALG11, UTP14C, RNASEH2B, DLEU7 , LECT1, PCDH8, OLFM4, PRR20A, PRR20B, PRR20C, PRR20D, PRR20E, PCDH17, TDRD3, and DIAPH3;
(iv) segment 4: MRE11A, CTSC, FAT3 , MTNR1B, SLC36A4, CCDC67, Cllorf75, KIAA1731, TAF1D, Cllorf54, MED17, VSTM5, HEPHL1, DYNC2H1,
RAB38, TMEM135, CEP57, USP35, GAB2 , MTMR2 , GUCY1A2, ANKRD49, PIWIL4, FUT4, AMOTL1, KDM4D, KDM4E, ENDOD1, SESN3, FAM76B, KCTD21, PANX1, DCUN1D5, NARS2, CNTN5 , AAMDC, INTS4, KCTD14, NDUFC2 -KCTD14 , THRSP, NDUFC2, ALG8, ARHGAP42 , TMEM133, PGR, TENM4, RP11-817J15.3, MMP27, RSF1, Cllorf53, Cllorf92, Cllorf93, POU2AF1, RP11-794P6.2 , BTG4,
Cllorf88, LAYN, SIK2, PPP2R1B, MMP8, MMP10, MMP1, MMP3, MMP13, ALG9, CWF19L2, ALKBH8, AP000889.3, TMEM123, MMP20, PDGFD, DDI1, FZD4, TRPC6, ANGPTL5, KIAA1377, Cllorf70, YAP1, BIRC3, BIRC2, RP11- 31506.2, MMP7, ALG9, FDX1 , ARHGAP20 , PRSS23, MSANTD4, KBTBD3,
AASDHPPT, TMEM126B, TMEM126A, CREBZF, CCDC89, SYTL2, AP000974.1, CCDC83, PICALM, EED, Cllorf73, CCDC81, ME3 , DLG2 , ZC3H12C, RDX, GRIA4, FAM181B, PRCP, Cllorf82, RAB30, PCF11, ANKRD42, CCDC90B, ELMOD1, Cllorf87, CASP12, CASP4, CASP5, CASP1, CARD16, CARD17, CARD18, Cllorfl, FDXACB1, Cllorf65, SLN, AP002353.1, AP001024.2, AP001024.1, SLC35F2, RAB39A, CRYAB, CUL5, ACATI , NPAT, ATM,
AP001925.1, KDELC2, EXPH5, DDX10, FOLR4, GPR83, HSPB2, DLAT, PIH1D2, Cllorf57, TIMM8B, SDHD, DIXDCl, HSPB2-Cllorf52 , Cllorf52, IL18, SDHD, TEX12, BC02 , and PTS;
(v) segment 5: SDAD1, AC110615.1, CXCL9, ART3, CXCL10, CXCL11, NUP54, SCARB2, FAM47E, STBD1, CCDC158, SHROOM3, SOWAHB, Sep-11,
CCNI, CCNG2, CXCL13, CNOT6L, MRPL1, AFM, AFP, ANXA3, BMP2K, PAQR3,
NAA11, GK2, ANTXR2, PRDM8 , FGF5, C4orf22, BMP3, PRKG2, RASGEF1B,
HNRNPD, HNRPDL, ENOPH1, TMEM150C, SCD5, SEC31A, THAP9, LIN54, COPS4, PLAC8, COQ2, HPSE, HELQ, MRPS18C, FAMI 75A, AGPAT 9 , NKX6-1, CDS1, WDFY3, COX18, ANKRD17, ALB, NAAA, RASSF6, IL8, CXCL6, PF4V1, CXCL1, PF4, PPBP, CXCL5, CXCL3, CXCL2, AC093677.1, FRAS1, BTC, PARM1, RCHY1, THAP6, C4orf26, CDKL2 , G3BP2, USOl, PPEF2, SLC4A4, GC,
NPFFR2, ADAMTS3, LPHN3, TECRL, UGT2B15, UGT2B10, UGT2A3, UGT2B7, UGT2B11, UGT2B28, UGT2B4, UGT2A1, SULT1B1, SULT1E1, CSN1S1, CSN2, STATH, HTN3, HTN1 , C4orf40, ODAM, FDCSP, CSN3, CABS1, SMR3A, SMR3B, PROL1, MUC7, AMTN, AMBN, ENAM, IGJ, UTP3, RUFY3, GRSF1, MOBIB , DCK, ARHGAP24, MAPK10, AFF1, UGT2B17, EPHA5, TMPRSSllBNL, TMPRSS11B, YTHDC1, TMPRSS11E, KLHL8, C4orf36, HSD17B13, HSD17B11, SLC10A6, NUDT9, RP11-9B6.1, PTPN13, SPARCL1, DSPP, DMP1, IBSP, MEPE, SPP1, PKD2, ABCG2, PPM1K, HERC6, HERC5, PYURF, HERC3, PIGY, NAP1L5,
FAM13A, TIGD2, GPRIN3, SNCA, MMRN1, GRID2, ATOH1, SMARCAD1 , HPGDS, PDLIM5, TMPRSS11F, RP11- 763F8.1 , FAM190A, BMPR1B, CPEB2, C1QTNF7, CC2D2A, FBXL5, FAM200B, BST1, CD38, FGFBP1, FGFBP2, PROM1 , TAPT1, LDB2, QDPR, CLRN2 , LAP3, MED28, FAM184B, DCAF16, NCAPG, LCORL, HAUS3, MXD4, ZFYVE28, RP11 -503N18.3 , RNF4, FAM193A, TNIP2, SH3BP2, ADD1, MFSD10, NOP14, GRK4 , HTT, MSANTD1, RGS12, HGFAC, DOK7, LRPAP1, AL590235.1, RP3-368B9.1, ADRA2C, OTOP1, TMEM128, LYAR, ZBTB49, NSG1, STX18, MSX1, CYTL1, STK32B, C4orf6, EVC2, EVC, CRMP1, C4orf50, JAKMIP1, WFS1, PPP2R2C, MAN2B2, MRFAP1, AC093323.1, S100P, MRFAP1L1, BLOC1S4, KIAA0232, TBC1D14, CCDC96, TADA2B, GRPEL1, SORCS2, PSAPL1, AFAP1, AC097381.1, ABLIM2, SH3TC1, HTRA3, ACOX3, TRMT44, GPR78, CPZ, HMX1, RAB28, NKX3-2, BOD1L1, POLN, WDR1 , ZNF518B, CLNK, HS3ST1,
SLIT2, PACRGL, KCNIP4, GPR125, GBA3, AC093917.1, PPARGC1A, DHX15, SOD3, CCDC149, LGI2, SEPSECS, PI4K2B, ZCCHC4, ANAPC4, SLC34A2, SEL1L3, C4orf52, RBPJ, CCKAR, TBC1D19, STIM2, RP11- 180C1.1 , WHSC2, C4orf48, NAT8L, WHSC1, UNC5C, TLR3, FAM149A, AC110771.1, CYP4V2, KLKB1, Fll, MTNR1A, FAT1, SORBS2, WWC2, CLDN22, CLDN24, CDKN2AIP, ING2, RWDD4, TRAPPC11, STOX2, ENPP6, IRF2, CASP3, CCDC111, MLF1IP, ACSL1, RP11-701P16.2, HELT, SLC25A4, KIAA1430, SNX25, LRP2BP,
ANKRD37, UFSP2, C4orf47, CCDC110, RP11 -27909.4 , PDLIM3, PDHA2, TENM3, and DCTD;
(vi) segment 6: KCTD12, IRG1, CLN5, FBXL3, MYCBP2, SCEL,
SLAIN1, C13orf45, LM07, COMMD6, UCHL3, and TBC1D4;
(vii) segment 7: EDNRB, POU4F1, RNF219, SPRY2, RBM26, NDFIP2,
SLITRK6, SLITRK5, IRS2, MY016, COL4A1, COL4A2, COL4A2-AS2, RAB20, CARKD, NALCN, ITGBL1, CARS2 , ING1, TM9SF2, CLYBL, GPC5, ZIC5, ZIC2, UBAC2, GPR18, GPR183, DAOA, FGF14, TEX30, KDELC1, BIVM, ERCC5, SLC10A2, EFNB2, ARGLU1, IP05, FARP1, RNF113B, STK24, SLC15A1, DOCK9, TPP2, METTL21C, CCDC168, OXGR1, MBNL2 , RAP2A, LINC00346, and
ANKRD10;
(viii) segment 8: FTSJD1, AP1G1, ATXN1L, IST1, ZNF821, IST1, DHODH, TXNL4B, HP, HPR, DHX38, PMFBP1, PHLPP2, MARVELD3 , CALB2, ZNF23, ZNF19, ZNF19, CHST4, and TAT;
(ix) segment 9: SORCS1, CYP2C18, CYP2C19, CYP2C9, CYP2C8,
NRG3, SORCS3, C10orfl29, PDLIM1, SORBS1, HELLS, GRID1, ALDH18A1, RP11-476E15.3, FAM190B, HPSE2, GHITM, C10orf99, CDHR1, LRIT2, LRIT1, RGR, HTR7, RPP30, ANKRD1, TCTN3, ENTPD1, C10orfl31, CC2D2B, CCNJ, BLNK, DNTT, OPALIN, TLL2, TM9SF3, PIK3AP1, LCOR, C10orfl2, SLIT1, ARHGAP19 , FRAT1, FRAT2, RRP12, AL355490.1, PGAM1 , EXOSC1, ZDHHC16 ,
MMS19, UBTD1, ANKRD2, HOGA1 , PI4K2A, PI4K2A, C10orf62, MOR 4 , AVPI1, MARVELD1, ZFYVE27, SFRP5, GOLGA7B, CRTAC1, AL358938.1, R3HCC1L, LOXL4, PYROXD2, HPS1, PCGF5, CNNM1 , GOT1, NKX2-3, SLC25A28, ENTPD7, CUTC, COX15, ABCC2, DNMBP, CPN1, ERLIN1, CHUK, PANK1 , CWF19L1, BLOC1S2, PKD2L1, SCD, WNT8B, SEC31B, NDUFB8, NDUFB8, HIF1AN, PAX2, FAM178A, SLC16A12, KIF20B, WAPAL, OPN4 , IFIT1B, IFIT1, IFIT5,
TBC1D12, PPP1R3C, TNKS2, FGFBP3, BTAF1 , HECTD2, CPEB3, CCDC147, SEMA4G, NOC3L, LIPA, MRPL43, Mar-05, MINPP1, PAPSS2, ATAD1, KLLN, PTEN, INPP5F, ANKRD22, STAMBPL1, ACTA2 , FAS, CH25H, IFIT2, IFIT3, IDE, TRUB1, MCMBP, SEC23IP, DPCD, POLL, FBXW4, FGF8, NPM3 , MGEA5, KCNIP2, FAM160B1, BTRC, ABLIM1, ATRNL1, RGS10, TIAL1, BAG3,
C10orf76, PPAPDC1A, C10orf85, KIF11, HHEX, EXOC6, CYP26C1, CYP26A1, MYOF, CEP55, 03FAR1, RBP4, PDE6C, FRA10AC1, LGI1, SLC35G1, PCGF6, TAF5, USMG5, XPNPEP1, GRK5, GPAM, TECTB, ACSL5, ZDHHC6, VTI1A, TCF7L2, HABP2, NRAP, CASP7, PLEKHS1, DCLRE1A, NHLRC2 , AL162407.1, ADRB1, C10orfll8, TDRD1, VWA2 , AFAP1L2, C10orf2, LZTS2, PDZD7, SFXN3, KAZALD1, HUG1, TLX1, LBX1 , RNLS, LIPJ, LIPF, LIPK, LIPN, LIPM, PLCE1, HPS6, LDB1, PPRC1, NOLC1, ELOVL3, PITX3, GBF1, NFKB2, PSD, FBXL15, CUEDC2, C10orf95, TMEM180, ACTR1A, SUFU, TRIM8, ARL3, SFXN2, WBP1L, CYP17A1, C10orf32, AS3MT, CNNM2 , NT5C2, INA, PDCD11, VAX1, KCNK18, SLC18A2, PDZD8, RP11 -451M19.3 , ADD3, MXI1, SMNDC1,
DUSP5, SMC3, RBM20, PDCD4, BBIP1, SHOC2, ADRA2A, TEX36, CALHM2, CALHM1, CALHM3, NEURL, FANK1 , DHX32, SFR1, WDR96, GSTOl, GST02, ITPRIP, CTBP2, EMX2, RAB11FIP2, FAM204A, SH3PXD2A, C10orfl37,
AL158835.1, MMP21, UROS, BCCIP, KIAA1598, OBFC1, COL17A1, SLK, CACUL1, NANOS1, EIF3A, FAM45A, SFXN4, PRDX3, OAT, NKX1-2, LHPP, RP11-12J10.3, FAM53B, METTL10, FAM175B, ZRANB1, WDR11, GPR26, CPXM2, EN04, PRLHR, CHST15, FGFR2 , ATE1, NSMCE4A, TACC2 , CCDC172, PNLIPRP3, PNLIP, PNLIPRP1, C10orf82, HSPA12A, BTBD16 , PLEKHA1, ARMS2 , HTRA1, DMBT1, C10orfl20, CUZD1, FAM24B, FAM24A, C10orf88, GFRA1 , PSTK, NPS, IKZF5, ACADSB, HMX3 , HMX2, BUB3, FOXI2, MGMT, AL355531.2, EBF3, GLRX3, MKI67, and PTPRE;
(x) segment 10: NTN5, FUT2, MAMSTR, RASIP1, IZUMOl, FUT1, FGF21, BCAT2, HSD17B14, PLEKHA4, PPP1R15A, TULP2, NUCB1, DHDH, BAX, FTL, GYS1, RUVBL2, LHB, CGB, CTB-60B18.6, CGB2 , CGB1, CGB5, CGB8, CGB7, NTF4, KCNA7 , SNRNP70, LIN7B, C19orf73, PPFIA3, HRC, TRPM4, SLC6A16, CCDC114, EMP3, TMEM143, SYNGR4, KDELR1, GRIN2D, GRWD1,
KCNJ14, CTC-273B12.7, CYTH2, LMTK3, SULT2B1, FAM83E, SPACA4, RPL18, SPHK2, DBP, CA11, AC011450.1, CD37, TEAD2 , DKKL1, CCDC155, PTH2, CTD-3148I10.1, SLC17A7, PIH1D1, ALDH16A1, CTD-3148I10.9, FLT3LG, RPL13A, RPS11, hsa-mir-150, FCGRT, RCN3, NOSIP, PRRG2 , PRR12, RRAS, SCAF1, IRF3, BCL2L12, PRMT1, ADM5 , CPT1C, TSKS, AP2A1, FUZ, MED25, PTOV1, PNKP, AKT1S1, TBC1D17, IL4I1, NUP62, SIGLECll, ATF5,
SIGLECll, VRK3, ZNF473, IZUM02, MYH14, KCNC3, NR1H2, NAPSA, POLD1, SPIB, SPIB, KPTN, NAPA, ZNF541, GLTSCR1, EHD2, GLTSCR2, SEPW1, TPRX1, MYBPC2, SLC8A2, FAM71E1, LRRC4B, EMC10, JOSD2, ASPDH, BBC3, CCDC9, PRR24, C5AR1, GPR77, DHX34, MEI S3 , NLRP13, SYT3, C19orf81, NLRP8, NLRP5, ZNF787, ZNF444, AC024580.1, GALP, ZSCAN5B, ZSCAN5C, ZSCAN5A, ZSCAN5D, AC006116.20, ZNF582, ZNF583, ZNF667, ZNF471, ZFP28, ZNF470, SHANK1 , CLEC11A, GPR32, ACPT, C19orf48, KLK1 , KLK15, KLK3, KLK2, AC037199.1, KLK4 , KLK5 , KLK6, KLK7 , KLK8 , KLK9, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14, CTU1, SIGLEC9, SIGLEC7, CD33,
SIGLECLl, IGLON5, VSIG10L, ETFB, CTD-2616Jll.il, CLDND2, NKG7, LIM2, CTD-2616J11.4, SIGLEC10, SIGLEC8, CEACAM18 , SIGLEC12, SIGLEC6, ZNF175, AC018755.il, HSPBP1, BRSK1, PPP6R1, TMEM150B, SUV420H2, SUV420H2, COX6B2, CTD-2105E13.6, FAM71E2, IL11, TMEM190, TMEM238, RPL28, UBE2S, SHISA7, ISOC2, ZNF628, NAT14, SSC5D, SBK2, SGK110, ZNF579, FIZ1, ZNF524, ZNF865, ZNF784, ZNF580, ZNF581, CCDC106,
U2AF2, EPN1, NLRP9, RFPL4A, PTPRH, TMEM86B, AC010327.2, SYT5, CTD- 2611012.2, NLRP11, NLRP4, SIGLEC5, SIGLEC5, TNNT1, TNNI3, CTD- 2587H24.4, DNAAF3, PPP1R12C, MYADM, PRKCG, CACNG7, CACNG8, CACNG6, VSTM1, TARM1, OSCAR, NDUFA3 , TFPT, PRPF31, CN0T3, LENG1, TMC4, MB0AT7, TSEN34, RPS9, LILRB3, LILRA6, LILRB5, LILRB2, LILRA3,
LILRA5, LILRA4, LAIR1, TTYH1, LENG8 , LENG9, CDC42EP5, LAIR2,
KIR3DX1, LILRA2, LILRB1, LILRA1, AC009892.10, LILRB4, KIR3DL1, KIR3DL3, KIR2DL4, KIR2DL3, KIR2DL1, KIR3DL2, FCAR, NCR1 , NLRP7, NLRP2, GP6, CTC-550B14.6, RDH13, EPS8L1, ZNF677, VN1R2, VN1R4, BIRC8, ZNF845, ZNF525, ZNF765, ZNF813, ZNF331, CTB-167G5.5, DPRX, NLRP12, ZNF615, ZNF701, SIGLEC14, HAS1, ZNF614, ZNF432, ZNF841, ZNF616, ZNF836, PPP2R1A, ZNF766, ZNF480, ZNF610, ZNF880, ZNF528, ZNF534, ZNF578, ZNF808, ERVV-1, ERVV-2, ZNF160, ZNF415, ZNF347, ZNF665, FPR2, ZNF321P, ZNF816, ZNF83, FPR1, ZNF611, ZNF600, ZNF28, ZNF468, ZNF320, ZNF577, ZNF649, ZNF613, ZNF350, and FPR3;
(xi) segment 11: NUP155, GOLPH3, WDR70, PDZD2, C5orf22,
PTGER4, TTC33, PRKAA1 , RPL37, CARD6, C7, HEATR7B2, C6, PLCXD3, MTMR12, OXCT1, C5orf51, FBX04, CCDC152, SEPP1, GHR, GDNF, EGFLAM, LIFR, AC091435.1, AC091435.2, OSMR, RICTOR, FYB, AC008964.1, C9, DAB2 , DROSHA, Mar-11, C5orf42, ANXA2R, ZNF131, ZFR, NIPBL, FBXL7, SLC1A3, CDH9, MRPS30, FAM134B, SPEF2, IL7R, CAPSL, UGT3A1, UGT3A2, LMBRD2, SKP2, NADKD1 , RANBP3L, SUB1, NPR3, AC026703.1, NNT, FGF10, TARS, ZNF622, NIM1, ADAMTS12 , RXFP3, SLC45A2, AMACR, C1QTNF3, RAI14, TTC23L, RAD1, BRIX1, DNAJC21, AGXT2, HMGCS1, CCL28, C5orf28,
C5orf34, PAIP1, PRLR, AC010368.2, PRDM9, MYO10, CDH10, C5orfl7, and CDH6;
(xii) segment 12: CNTLN and CCDC171;
(xiii) segment 13: SNURF, AVEN, CHRM5, EMC7 , PGBD4, KATNBL1, EMC4 , GJD2, ACTC1, AQR, ZNF770, AC114546.1, GABRB3, GABRA5, GABRG3, UBE3A, ATP10A, ATPBD4, TMC05A, RYR3, SPRED1, FAM98B, RASGRP1,
C15orf53, C15orf54, THBS1, FSIP1, C15orf41, C15orf23, IVD, SQRDL, CHST14, CASC4, CTDSPL2, EIF3J, RP11-82I10.1 , PHGR1, DISP2, MEIS2 , MEX3B, RP11-597K23.2, SQRDL, TMC3, SPG11, SPATA5L1, C15orf48,
SLC30A4, BLOC1S6, STARD5, BAHD1, GATM, TRIM69, C15orf43, HOMER2 , FAM103A1, C15orf40, BTBD1, TM6SF1, HDGFRP3, BNC1, TMED3, KIAA1024, MTHFS, ST20-MTHFS, ST20, C15orf37, C150RF37, BCL2A1, ZFAND6, FAH, KLHL25, LRRC57, HAUS2, STARD9, CDAN1, TTBK2, AC015660.1, LYSMD4,
DKFZP779J2370, CTD-2054N24.2 , ADAMTS17, C15orf57, MEF2A, SLC28A2, WHAMM, SORD, DUOX2 , DUOXA2 , DUOXA1 , DUOX1, SHF, SNAP23, AGBL1, C15orf52, ARRDC4, AP3B2, FSD2, CHRNA3 , CHRNB4, ADAMTS7, MORF4L1, CTSH, RASGRF1, ANKRD34C, ZFP106, CHRNA5 , PLCB2 , IREB2, AGPHD1, AC027228.1, PSMA4, TTLL13, RP11-697E2.6, NGRN, GABARAPL3, ZNF774, IQGAP1, CRTC3, BLM, FURIN, FES, MAN2A2, UNC45A, HDDC3, RCCD1, PRC1, VPS33B, C15orf56, RP11-133K1.2, PAK6 , IL16, ANKRD63, GPR176,
EIF2AK4, SRP14, RP11-210M15.2 , ARNT2, FAM108C1, KIAA1199, RP11- 351M8.1, MESDC2, MESDC1, C15orf26, PATL2, B2M, SV2B, PPP1R14 D, SPINT1, RHOV, VPS18, DLL4, CHAC1, LRRC28, AC022819.4, RPUSD2, BMF, BUB1B , ZFYVE19 , MCTP2, AC016251.1, NR2F2, AC087477.1, SPATA8 ,
GDPGP1, CHD2, RGMA, AC112693.2, ZNF710, IDH2, SEMA4B, CIB1, FKSG62, FAM82A2, TTC23, DNAJC17, FAM174B, CASC5, SYNM, GCHFR, C15orf62, INO80, EXD1, CHP1, OIP5, NUSAP1, NDUFAF1, RTF1, ITPKA, LTK, RPAP1, CAPN3, PGPEP1L, WDR61, and CRABP1;
(xiv) segment 14: C21orf37, C21orf91, CXADR, BTG3, USP25,
CHODL, KRTAP21-3, KRTAP21-2 , KRTAP21-1, KRTAP8-1, KRTAPll-1,
KRTAP19- 6 , KRTAP19-7 , KRTAP22-2, KRTAP6-3, KRTAP6-2, KRTAP22-1, KRTAP6-1, KRTAP20-1, KRTAP20-4, KRTAP20-2 , KRTAP20-3 , KRTAP19-1 , KRTAP19-2 , KRTAP19-3 , KRTAP19-4 , KRTAP19-5 , CBR1, CBR3, DOPEY2, MORC3, SETD4, SOD1, SCAF4, CHAF1B, CLIC6, AP000695.1, HUNK, MIS18A, MRAP, URB1, C21orfll9, AP000688.1, CLDN14, KCNE2, FAM165B,
AP000322.54, AP000322.53, EVA1C, KRTAP19-8 , TCP10L, C210RF59,
C21orf59, and SYNJ1;
(xv) segment 15: XKR9, RP11-758M4.1 , PI15, CRISPLD1, HNF4G, PEX2, and GDAP1; and
(xvi) segment 16: ZNF724P, ZNF91, ZNF66P, ZNF626, ZNF730, ZNF98, ZNF492, and ZNF99.
Preferably, the genomic segments are as set forth in Tables 1 and 2.
In some cases, determining the CNA status of each genomic segment comprises determining the copy number of all of said loci within each genomic segment. In some cases, copy number aberration CNA status is determined for not more than 50, not more than 30, not more than 20 or not more
than 16 genomic segments, totalling not more than 600 megabases (600 Mbp) in length. The present inventors have found that a relatively compact signature (such as that provided by the CNA profile of the 16 segments detailed herein) is sufficient to provide highly accurate classification of previously unknown samples into the chemosensitive or the chemorefractory class. The provides
considerable efficiency savings in comparison with analysing CNA status for the entire genome or for all chromosomes other than X and Y, which would entail determination over some 3000 Mbp. In some cases, the sample is classified as being chemosensitive and the method further comprises the step of selecting or recommending the subject for a course of chemotherapy for SCLC. The chemotherapy may be any suitable therapy, including combination therapy, for the treatment of SCLC. In particular, the chemotherapy may comprises a platinum-based chemotherapeutic, optionally cisplatin, carboplatin or oxaplatin. Additionally or alternatively, the chemotherapy may comprise etoposide. The chemotherapy may comprise a platinum-based chemotherapeutic, optionally cisplatin, in combination with
etoposide whether administered simultaneously, sequentially or separately.
In some cases the sample is classified as being chemorefractory, and the method further comprises the step of selecting or recommending the subject for treatment other than chemotherapy with a platinum- based chemotherapeutic and/or etoposide. For example, the treatment other than chemotherapy with a platinum-based chemotherapeutic and/or etoposide may comprises alternative or experimental therapy, optionally enrolment in a clinical trial for an experimental SCLC treatment. Examples of treatments being developed for SCLC are discussed in (6), the entire contents of which is expressly
incorporated herein by reference.
In some cases, the method of the present invention further comprises the step of providing a prognosis of the likely course of the subject's SCLC based on the classification of the sample as being chemosensitive or chemorefractory . In particular, the prognosis may
include an estimate of progression-free survival (PFS) time and/or overall survival (OS) time.
In some cases in accordance with the method of the present
invention, determining the CNA status of said at least 10 genomic segments of said CTC sample comprises a step of next-generation sequencing (NGS) of DNA obtained from said CTC sample or amplified from said CTC sample. NGS may, for example, comprise Illumina® MiSeq® sequencing.
In some cases in accordance with the method of the present
invention, DNA obtained from said CTC sample may amplified by whole genome PCR, e.g. using an Amplil™ WGA kit (Silicon Biosystems) .
In some cases in accordance with the method of the present
invention, the CTC sample is obtained from a blood sample taken from said subject. Typically, the blood sample is processed to enrich and/or isolate CTCs, e.g. using the CellSearch™ Circulating Tumour Cell kit (Janssen Diagnostics®) . In particular, processing said blood sample to enrich and/or isolate CTCs may employ markers selected from the group consisting of:
CD45-;
EpCAM+; and
cytokeratins 8, 18+, and/or 19+.
In some cases in accordance with the method of the present
invention, determining the CNA status of said at least 10 genomic segments of said CTC sample comprises comparing CTC copy number with a germline control obtained from the same subject. The germline control is a cell type other than the SCLC tumour cell or the CTC. Conveniently, the germline control comprises DNA obtained from a white blood cell (WBC) sample or amplified from said WBC sample.
In some cases in accordance with the method of the present
invention, the subject has been diagnosed as having SCLC.
In some cases in accordance with the method of the present invention, the subject has not completed a course of chemotherapy for SCLC. In particular, the subject may not have started a course of chemotherapy for SCLC. The example described herein found that the 16 segment CNA profile classified according to intrinsic or pre- treatment chemosensitivity . Accordingly, the method of the present invention is in some cases best suited to predicting chemosensitive or chemorefractory status of a treatment naive patient.
In a second aspect, the present invention provides a method for stratifying a population of subjects according to SCLC
chemosensitivity, the method comprising carrying out the method of the first aspect of the invention on each of the subjects in the population. This method finds particular application to the identification of patients for personalised medicine and/or clinical trials. Patients classified as chemorefractory are expected to have intrinsic drug resistance to cisplatin/etoposide chemotherapy, and therefore to have a particular need for alternative therapeutic options .
In a third aspect, the present invention provides a system for carrying out the method of the first or second aspect of the present invention, the system comprising:
a computer-readable storage medium which stores computer- executable instructions for applying a computational classifier to a dataset comprising one or more sample CNA profiles, said
computational classifier comprising a machine learning model trained on a set of training CNA profiles of at least 10 genomic segments obtained from training samples of known
chemosensitive/chemorefractory status, which training samples include at least two known chemosensitive SCLC CTC samples and at least two known chemorefractory SCLC CTC samples; and
a processor which is configured to perform steps comprising receiving said dataset and executing said computer-executable instructions stored in said computer-readable storage medium,
wherein said at least 10 genomic segments are selected from the group of genomic segments consisting of:
Segment-1: chromosome 16, start: 53467889, end: 87739290;
Segment-2 : chromosome 18, start: 2537524, end: 76762677;
Segment-3: chromosome 13, start: 21547171, end: 61148012;
Segment-4: chromosome 11, start: 77371041, end: 112140678;
Segment-5: chromosome 4, start: 1873151, end: 187647876;
Segment-6: chromosome 13, start: 75858808, end: 78338377;
Segment-7: chromosome 13, start: 78469616, end: 111567416;
Segment-8: chromosome 16, start: 71315292, end: 72210777;
Segment-9: chromosome 10, start: 83635070, end: 131982785;
Segment-10: chromosome 19, start: 47724081, end: 57100279;
Segment-11: chromosome 5, start: 15500305, end: 44820530;
Segment-12: chromosome 9, start: 15552895, end: 17503921;
Segment-13: chromosome 15, start: 25200133, end: 100882210;
Segment-14: chromosome 21, start: 17102344, end: 37860058;
Segment-15: chromosome 8, start: 71581600, end: 77913280; and
Segment-16: chromosome 19, start: 20802867, end: 23578362,
wherein said start and end positions are according to the numbering system of Genome Reference Consortium GRCh37, patch release 13, dated 28 June 2013.
In some cases, the computational classifier comprise a SVM or a PLS regression. In particular, the computational classifier may comprise a Gaussian Radial Basis kernel function. In particular, the parameters that support the classifier may be as follows:
parameter : cost C = 0.25
Hyperparameter : sigma = 0.0476184222095904
Number of Support Vectors : 43. In some cases, the system further comprises an output module configured to output the chemosensitive/chemorefractory
classification of the or each CNA profile in the dataset. The output module may take the form of a display, print out or network terminal for displaying the chemosensitive/chemorefractory
classification of the or each CNA profile in the dataset.
The present invention includes the combination of the aspects and preferred features described except where such a combination is clearly impermissible or is stated to be expressly avoided. These and further aspects and embodiments of the invention are described in further detail below and with reference to the accompanying examples and figures.
Brief description of the figures
Figure 1 shows A) an example of DEPArray images of single CTCs isolated from the blood of patients with SCLC. Following isolation and WGA a QC-PCR assay was used to determine the genome integrity of each sample with 0-4 bands determining the overall integrity of each sample. Single CTCs (sCTC), pools of 10 CTCs (pCTC) and pools of WBCs (pWBC) were processed using the same protocol. B) A heat map showing copy number profiles of 13 genes found to amplified or deleted in SCLC tumours in 80 baseline CTCs with corresponding CNA described by Rudin et al . (2) or Peifer et al . (3) . Hierarchical clustering of the CTCs based on the 13 recurrent aberrations failed to separate chemosensitive and chemorefractory patients. Figure 2 shows A) Global CNA analysis of 80 CTCs from 4
chemorefractory (purple) and 6 chemosensitive (green) patients showing areas of chromosomal gains (red) and loss (blue) based on 6,360 cancer related genes. Common regions of amplification and deletion are indicated by red and blue triangles. B) Left panel shows PCA of CNA data with separation of individual CTCs from chemosensitive (green) and chemorefractory (purple) patients CTCs. Individual CTCs are coloured in a patient specific manner and the percentage variance for each of the principal components is given in parenthesis. Right panel shows the correlation between the PCI component of averaged CNA and OS for each of the 10 SCLC patients. C) A heatmap showing CNA of 16 predictor segments for 71 baseline CTC samples, amplified segments are shown in red, deleted segments shown in blue. Hierarchical clustering showed strong grouping of chemosensitive (green) and chemorefractory (purple) samples, with an
increased level of amplification obvious m the chemosensitive samples .
Figure 3 shows A) chromosomal copy number changes of six CDX models derived from 2 chemorefractory (purple) and 4 chemosensitive (green) patients. Areas of chromosomal gains (red) and loss (blue) based on 6,360 cancer related genes are shown. Location of common SCLC deletions (3p, 17p) and amplification (3q, 5p) are indicated by blue and red triangles. B) The 16 segment predictive signature correctly classified 6 out of 6 CDX samples using two classifiers (PLS and S V) , giving an accuracy of 100%.
Figure 4 shows A) the timeline of treatment regimes of the 5 baseline chemosensitive patients showing times of collections of pre-treatment blood samples and relapse blood samples. Filled blue arrows indicating time of CTC collections. B) Global CNA analysis of CTCs from 5 baseline chemosensitive patients at baseline pre- treatment (green boxes) and at relapse (pink boxes) . Areas of chromosomal gains (red) and loss (blue) based on 6,360 cancer related genes are shown. Common regions of amplifications and deletions are indicated by red and blue triangles . C) PCA of averaged CTC CNA data from baseline and relapse showing samples clustering in a patient-specific manner but with no clear separation of CTC CNA at baseline and at relapse. D) CNA (blue= loss, red=gain) of the 16 predictor segments of all CTC samples analysed in this study. CTC samples at baseline (pre-treatment) from patients who were subsequently chemosensitive are labelled with the green bar. Samples taken at relapse with chemoresistant disease from initially chemosensitive patients are labelled with the pink bar. Samples taken at baseline (pre-treatment) from patients who were
subsequently chemorefractory are labelled with the purple bar.
Detailed description of the invention
In describing the present invention, the following terms will be employed, and are intended to be defined as indicated below.
"Small Cell Lung Cancer" ("SCLC") or "Small Cell Lung Carcinoma" is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract.
"Chemosensitive" as used herein refers to SCLC disease of patients who progress more than 90 days after completion of chemotherapy (1 17), for example platinum/etoposide chemotherapy. In particular, "chemosensitive" in this context means intrinsically sensitive to chemotherapy; the disease may acquire drug resistance during or as result of chemotherapy.
"Chemorefractory" as used herein refers to SCLC disease of patients who progress within 90 days of completion of chemotherapy (16, 17), for example platinum/etoposide chemotherapy. In this context, chemorefractory disease indicates intrinsic drug resistance and is to be distinguished from initially chemosensitive disease that acquires drug resistance as a result of chemotherapy, i.e. acquired drug resistance.
"Circulating Tumour Cells" ("CTCs") are cells that have shed into the vasculature from a primary tumour and circulate in the
bloodstream. CTCs derived from SCLC have been detected based on expression of epithelial cell adhesion molecule (EpCAM) and
cytokeratins (1) . CTCs therefore provide a "liquid biopsy" of SCLC and which is of prognostic significance.
"Copy Number Aberration" ("CNA") or "Copy Number Alteration" ("CNA") as used herein are changes in copy number, i.e. gain or loss, that have arisen in somatic tissue, for example in a tumour. The term copy number variations (CNVs) is also used, but more commonly describes germline changes in copy number. CNA has been detected in a variety of cancers, including SCLC (1) . CNAs may be detected using copy number analysis by a variety of techniques, including next-generation sequencing (NGS) . CNAs can be limited to a single gene or include a contiguous set of genes, and can for example range in size from around 1 kilobase to several megabases.
"Subject" as used herein is a human being. The subject may in some cases be a smoker or former smoker. However, it is specifically contemplated herein that the subject may be a non-smoker. The subject may, in some cases, have been diagnosed as having SCLC, suspected as having SCLC or considered at risk of developing SCLC.
"Support Vector Machine" ("SVM") is a machine learning algorithm to classify data. Given a set of training examples, each marked for belonging to one of two categories, an SVM training algorithm builds a model that assigns new examples into one category or the other. An SVM model is a representation of the examples as points in space, mapped so that the examples of the separate categories are divided by a clear gap that is as wide as possible. New examples are then mapped into that same space and predicted to belong to a category based on which side of the gap they fall on. An SVM classifier, described further herein, has been trained on CNA profiles of known chemosensitive/chemorefractory status, and may therefore be employed to classify the CNA profile of an unknown sample as being from a chemosensitive or a chemorefractory subject.
"Principal Components Analysis" ("PCA") is an exploratory
multivariate statistical technique for simplifying complex data sets. Given m observations on n variables, the goal of PCA is to reduce the dimensionality of the data matrix by finding r new variables, where r is less than n. Termed principal components, these r new variables together account for as much of the variance in the original n variables as possible while remaining mutually uncorrelated and orthogonal. Each principal component is a linear combination of the original variables, and so it is often possible to ascribe meaning to what the components represent.
The following is presented by way of example and is not to be construed as a limitation to the scope of the claims.
Examples
Example 1 - Molecular analysis of circulating tumour cells
identifies distinct profiles in chemosensitive and chemorefractory patients with small cell lung cancer Introduction
Most patients with small cell lung cancer (SCLC) , a metastatic, aggressive disease are initially chemosensitive but relapse with acquired chemoresistance . Some patients (~20%) , defined as
chemorefractory, relapse within 3 months of initial treatment.
Molecular mechanisms differentiating chemosensitive from
chemorefractory disease are unknown. We examined circulating tumour cell (CTC) copy number aberrations (CNA) in pre-treatment blood samples to determine their potential as a minimally invasive biomarker to predict chemosensitive versus chemorefractory disease. Analysis of 80 CTC samples from 10 patients generated a CNA
classifier correlating with subsequent response and relapse that was verified in 6 independent SCLC patient-derived CTC explants.
Longitudinal analysis of CTC CNA from 5 chemosensitive patients who subsequently relapsed and did not respond to chemotherapy
rechallenge, failed to recapitulate baseline changes between chemosensitive and chemorefractory disease suggesting different underlying resistance mechanisms. These data highlight CTC utility to interrogate drug resistance and potentially, stratify patients according to predicted chemosensitivity in clinical trials of novel therapeutics.
Methodology
Patients and Clinical Samples
Patients with SCLC were consented to the CHEMORES (CHEMOtherapy RESistance) study, a prospective biomarker programme for the investigation of blood-borne biomarkers in lung cancer. The study had been prospectively approved by the local Research Ethical
Committee (REC reference 07/H1014/96) . Clinical data including age, smoking status, histological subtype and clinical outcomes was also collected .
CTC Enrichment and Enumeration and isolation
Blood samples were collected in 10 ml CellSave preservative
vacutainers and stored at room temperature for up to 96 hours. The blood samples were then processed using the CellTracks® AutoPrep® system, the CellSearch™ Circulating Tumour Cell kit and the
CellTracks® Analyser II (Janssen Diagnostics®) according to the manufacturer's instructions. After scanning on the CellTracks® Analyser II system the cartridges used during the CellSearch CTC enumeration were removed from the MagNest™ device and stored in the dark at 4°C prior to further processing. Both single and groups of cells were isolated using the DEPArray system (Silicon Biosystems) according to the manufacturer's instructions.
Whole Genome /Amplification of CTC DNA & Quality Control Assay
Whole genome amplification (WGA) was performed using the Amplil™ WGA kit version 01 (Silicon Biosystems) according to the manufacturer's instructions to generate a 50 μΐ WGA product. Initial lysis was performed at 42 °C with the proteinase K containing lysis reaction mix for a minimum of 15 hours before the proteinase K was
inactivated by heating to 80°C for 10 min. The DNA was then digested into smaller fragments at 37 °C for 3 hours using an MSEI restriction endonuclease prior to Amplil™ adapter ligation and PCR
amplification. All WGA products were purified post-amplification using the High Pure PCR Product Purification® kit (Roche) .
The quality of the WGA product was determined using the Amplil™ QC kit (Silicon Biosystems) as per the manufacturer's instructions. A multiplex PCR to assess 4 amplicons of different lengths in
chromosomes 5q, 6q, 12p and 17p was performed and visualised on a 1% agarose gel.
DNA Library Preparation and Next Generation Sequencing
The WGA products (250 ng) were MSEI (New England BioLabs) digested to remove the Amplil amplification primers then purified with the High Pure PCR Product Purification kit (Roche) followed by
sonication with the Bioruptor UCD-200 (Diagenode) for 11 cycles (30
sec. on, 30 sec. off) to produce fragments of 300 - 350 base pairs in length. DNA libraries were prepared using NEBNext® Ultra™ DNA Library Prep Kit For Illumina® (New England BioLabs) with 50 ng of DNA added per library preparation. The samples were processed according to the manufacturer's instructions.
WGS of the CTCs and WBCs was carried out on the Illumina® MiSeq® desktop sequencer (Illumina) . The MiSeq reagent kit V2 (300 cycles) was used with the MiSeq® desktop sequencer with 11 to 15 samples multiplexed to be sequenced together.
Copy Number Aberration analysis from WGS data
Illumina MiSeq® whole genome data for CTCs and WBCs were aligned to the human genome using SMALT. Copy number alterations in the data were identified using FREEC (20) with an adaptive window size.
Mappability data for HG19 with an edit distance of 1 were downloaded from the FREEC web site
(http://bioinfoout.curie.fr/projects/freec/) . An estimated copy number was assigned to all the protein coding genes of the human genome (version hgl9) in each sample. The weighted mean of the overlapping copy number estimates (as computed by FREEC) that map to the given loci was calculated. FREEC predicted copy number data was averaged across loci, and both median and predicted copy number data were imported into MeV (21) to generate the Principal Component Analysis (PCA) data (median centring mode with recommended MeV algorithm) . The copy numbers were also mapped to genome coordinates using the Bioconductor package annmap to provide ENSEMBL version 70 annotation (22) . For generation of genome-wide CNA profiles the CNA data for 6,360 cancer-related genes was clustered in MeV using Pearson Correlation average linkage.
Identification of Cancer-Related Genes
On 3rd February 2014 the geneRIF database was downloaded from the NCBI web site (ftp://ftp.ncbi.nlm.nih.gov/gene/GeneRIF/) . All human genes with RIF text containing at least one of the 10 key words or word stems ("carcinogen", "cancer", "carcinoma", "tumor",
"leukemia", "tumour", "oncogen", "leukaemia", "oncolog", "malignan")
were considered cancer-related. In total 6,682 cancer-related protein-coding genes were identified by mapping ENSEMBL gene ID and gene symbol in the geneRIF database to ENSEMBL (v70) . Only autosomal chromosomes were used in CNA analysis so 268 genes on the X, Y or mitochondrial chromosome and were removed from the list leaving a total of 6,414 cancer-related genes.
Quality Control Analysis of Copy Number Alteration Data
The Illumina MiSeq data from 48 WBC samples, processed alongside the CTC samples, which had been subjected to WGA and NGS, was analyzed for CNA at the cancer-related gene level and protein-coding gene level to identify potentially unreliable loci. A locus was called potentially unreliable if it was lost or amplified in more than 16 of the 48 samples (greater than 33%) . In total 0.84% of the cancer- related genes and 0.96% of protein-coding genes were removed from further analysis.
Generation of 16 segment predictive classifier
LIMMA analysis of 71 samples (after excluding Patient 1) identified 2183 genes (see Table 1) as having significantly different copy number profiles between chemosensitive and refractory samples at 1% FDR. These genes were collapsed down to 16 unique profiles based on their genomic locations and copy number changes . The inventors next developed a predictive model based on the 16 CNA segments using a radial basis support vector machine (SVM) algorithm and a repeated 10-fold crossvalidation approach to tune model parameters and evaluate performance in the training samples. The classifier achieved an average accuracy of 100% and standard deviations of 0 for the 100 repetitions, suggesting that prediction performances of the 16 CNA predictors were highly consistent.
Results
The present inventors performed CNA analysis of 80 CTC samples from 10 SCLC patients, including four classified as chemorefractory and six as chemosensitive. CTCs from each patient were enriched and enumerated using the CellSearch™ platform and CTC numbers ranged
from 27-20815 per 7.5ml blood (median 414) . Individual CTCs or pools of CTCs and white blood cells (WBCs) were isolated using a Silicon Biosystems DEPArray™ system (Figure la) . A total of 104 baseline samples were isolated for CNA analysis; 68 single CTCs (2-10 per patient), 12 pools of 10 CTCs, 12 single WBCs and 12 pools of 10 WBCs. DNA from each of these 104 isolated cell samples underwent whole genome amplification (WGA) with quality control PCR (QC-PCR) confirming that >90% of samples had a Genome Integrity Index (Gil) ≥2 (11) . Next Generation Sequencing (NGS) libraries were generated for all samples and low resolution Whole Genome Sequencing (WGS) performed. A bioinformatics pipeline was developed to enable CNA analysis of WGS data with WBCs from individual patients' used as germline controls.
Analysis of 13 genes frequently amplified or deleted in SCLC in the isolated CTC WGA products was consistent with the results from previous studies of SCLC tissue (5,6) (Figure lb), with CTC specific gains and loss seen in all patients. Analysis of a wider gene panel showed similar results reinforcing that CTC derived genetic profiles are a clinically relevant surrogate for tumour tissue. We next performed unsupervised hierarchical clustering based on the 13 genes to determine any association with the chemosensitive or chemorefractory status of donor patients. Although there was heterogeneity amongst the 13 gene signature, there was no obvious clustering of pre-treatment samples from chemosensitive patients separately from chemorefractory patients (Figure lb) .
We next extended our analysis to genome-wide CNA profiles of individual CTCs and identified previously reported common regions of both gain (3q, 5p) and loss (3p, 13q, 17p) across patients (Figure 2a), (5,6,7) . To determine whether there are significant differences in global-chromosomal alterations between chemosensitive and chemorefractory patients' CTCs, CNA data from all 80 CTC samples was analysed in an unsupervised PCA (Figure 2b) . There was clear separation of chemosensitive and chemorefactory CTC samples, indicating CNA differences as a potential biomarker of
chemoresponse . To further assess this association between CTC CNA
profiles and patient outcomes, a second PCA was performed using an averaged value for each individual patient's CTC CNA (Figure 2b) . This analysis demonstrated a correlation between the largest principal component (PCI) and overall survival (OS) in this patients group with the exception of Patient 1, who could not be accurately classified due to death from intercurrent infection within three months of initial response to treatment . Because of this ambiguity in classifying Patient 1, all Patient 1 data was omitted from further analysis.
We next used the global CTC-derived CNA data that discriminated chemosensitive/chemorefractory patients as a training data set to generate a predictive signature. Using bioinformatic approaches, including LIMMA (12), we identified 2183 loci that exhibited significant differential copy number changes between chemosensitive and chemorefractory CTC samples (FDR < 1%) . These loci were grouped according to chromosomal location and CNA status to generate a set of 16 CNA segments that stratified CTC samples from chemosensitive and chemorefractory patients. Of the 16 segments, 10 were amplified in CTCs from chemosensitive patients compared to those from
chemorefractory patients. Unsupervised, hierarchical clustering of CNA profiles of the 16 predictor segments for baseline CTC samples demonstrated strong grouping according to chemosensitive or
chemorefractory status, as expected (Figure 2c) .
Based on the 16 CNA segments, we developed a predictive model using a radial basis support vector machine (SVM) algorithm and a repeated 10-fold cross-validation approach to tune model parameters and evaluate performance in the initial 10 SCLC training samples. We verified performance of the resulting classifier in an independent test set of SCLC CDX tumours derived from an additional six patient donors with chemosensitive (n=4) and chemorefractory (n=2) disease. DNA was extracted at first passage of each CDX tumour and subjected to low resolution WGS CNA analysis. Genome wide analysis of CNA of each CDX tumour revealed typical SCLC associated profiles (Figure 3a) . When the 16 loci classifier was applied to this independent
test set, 6 out of the 6 CDX tumours were classified correctly (Figure 3b) .
A major advantage of CTC profiling is routine availability of longitudinal samples to investigate tumour evolution and acquired mechanisms of chemoresistance . In patients with chemosensitive SCLC who relapse or progress after first line treatment, the response rate to second line therapy is lower (~25%) than for first line treatment (~70%) (13, 14, 15) . Mechanisms of this acquired
chemotherapy resistance are unknown. Two of the five initially chemosensitive patients (patients 6 and 10) progressed during 2nd line treatment, an additional patient (patient 5) progressed within 3 months of 2nd line treatment, one patient progressed during 3rd line treatment (patient 8), and the remaining patient (patient 4) did not receive 2nd line treatment due to clinical deterioration such that they were unfit for further treatment at relapse. To ask whether the drug resistance phenotype at relapse is reflected by either the same CNA changes observed in CTCs from patients with initially chemorefractory disease, or from additional CNA changes that emerge during treatment and relapse, we examined CTCs obtained at relapse from these five patients (Figure 4a) . For the relapse samples, a total of 48 CTC samples (40 single CTCs, 8 pools of 10 CTCs) and 15 WBCs controls (10 singles and 5 pools) were isolated and CNA profiles generated to compare with their corresponding baseline CTCs samples. No obvious consistent global changes were observed between CTCs isolated at relapse and at baseline prior to any treatment (Figure 4b) . Unsupervised clustering of pre-treatment and progression data sets demonstrated patient-specific clustering, but no clustering according to whether pre-treatment or on
progression sampling (Figure 4c) .
Though no de novo global chromosomal changes were observed in samples obtained on progression, we next asked whether loci
associated with intrinsic chemosensitivity were significantly altered. To this end, CNA data at progression were analysed using the 16 segment, predictive classifier generated from pretreatment samples. However, 43 of the 48 CTCs isolated at progression remained
classified as chemosensitive with the CNA profiles showing similar patterns of amplification and deletion at both baseline and relapse (Figure 4d) . These data strongly imply that the genetic alterations linked with intrinsic drug resistance are different from that seen during relapse of initially chemosensitive patients.
Current clinical criteria used to segregate patients with either chemosensitive or chemorefractory disease are somewhat arbitrary, based on the time to progression (16, 17), rather than any molecula: characteristics associated with drug resistance mechanisms. As our molecular understanding of this aggressive disease evolves, we anticipate that more precise molecular classification of SCLC patients will emerge and the minimally invasive CTC profiling approach presented here can be viewed as a formative step in this development. We suggest that due to the iatrogenic effects of chemotherapy seen in some cancers (18, 19), prior knowledge of the likely patient benefit of standard of care chemotherapy may aid management of SCLC patients. To this end, further qualification in larger patient cohorts of the CTC CNA based classifier described here is warranted. The decision not to treat patients with a robust baseline chemorefractory molecular signature, avoiding nontrivial toxicities of platinum/etoposide requires serious consideration. In particular, it may become applicable as improved and/or alternative treatments emerge from ongoing/upcoming early clinical trials of novel agents targeting e.g., SCLC stem cells, DNA damage repair and epigenetic regulators (6) .
Table 1: 2183 loci of predictive signature grouped into 16 segments
Gene symbol Ensembl ID Chromosome Start End Strand
SEGMENT-1
RBL2 ENSG00000103479 16 53467889 53525561 +
AK IP ENSG00000166971 16 53525291 53538323 -
RPGRIP1L ENSG00000103494 16 53631595 53737850 -
FTO ENSG00000140718 16 53737875 54155853 +
RP11-324D17.1 ENSG00000259517 16 54279456 54304658 -
IRX3 ENSG00000177508 16 54317216 54320675 -
IRX5 ENSG00000176842 16 54964774 54968397 +
IRX6 ENSG00000159387 16 55357672 55364672 +
MMP2 ENSG00000087245 16 55423612 55540603 +
LPCA 2 ENSG00000087253 16 55542910 55620582 +
CAPNS2 ENSG00000256812 16 55600584 55601599 +
SLC6A2 ENSG00000103546 16 55689516 55740104 +
CES1 ENSG00000198848 16 55836763 55867249 -
CES5A ENSG00000159398 16 55880066 55989943 -
GNA01 ENSG00000087258 16 56225302 56391356 +
AMFR ENSG00000159461 16 56395364 56459450 -
NUDT21 ENSG00000167005 16 56463045 56486111 -
0GF0D1 ENSG00000087263 16 56485402 56513012 +
BBS2 ENSG00000125124 16 56500748 56554195 -
M 4 ENSG00000102891 16 56598961 56602869 +
M 3 ENSG00000087250 16 56622986 56625000 +
MT2A ENSG00000125148 16 56642111 56643409 +
MT1E ENSG00000169715 16 56659387 56661024 +
AC026461.1 ENSG00000268317 16 56662971 56666150 -
MT1M ENSG00000205364 16 56666145 56667898 +
M 1A ENSG00000205362 16 56672578 56673999 +
MT1B ENSG00000169688 16 56685811 56687116 +
MT1F ENSG00000198417 16 56691606 56694610 +
MT1G ENSG00000125144 16 56700643 56701977 -
MT1H ENSG00000205358 16 56703726 56705041 +
MT1X ENSG00000187193 16 56716336 56718108 +
NUP93 ENSG00000102900 16 56764017 56880792 +
SLC12A3 ENSG00000070915 16 56899119 56949762 +
HERPUD1 ENSG00000051108 16 56965960 56977798 +
CETP ENSG00000087237 16 56995762 57017757 +
NLRC5 ENSG00000140853 16 57023397 57117443 +
Gene symbol Ensembl ID Chromosome Start End Strand
CPNE2 ENSG00000140848 16 57126449 57181878 +
FAM192A ENSG00000172775 16 57186378 57220028 -
RSPRY1 ENSG00000159579 16 57220049 57274387 +
ARL2BP ENSG00000102931 16 57279010 57287516 +
PLLP ENSG00000102934 16 57290004 57318599 -
CCL22 ENSG00000102962 16 57392684 57400102 +
CX3CL1 ENSG00000006210 16 57406370 57418960 +
CCL17 ENSG00000102970 16 57438679 57449974 +
CIAPIN1 ENSG00000005194 16 57462081 57481440 -
COQ9 ENSG00000088682 16 57481337 57495187 +
POLR2C ENSG00000102978 16 57496299 57505922 +
DOK4 ENSG00000125170 16 57505863 57521239 -
CCDC102A ENSG00000135736 16 57546090 57570511 -
GPR114 ENSG00000159618 16 57576333 57625593 +
GPR56 ENSG00000205336 16 57644564 57698944 +
GPR97 ENSG00000182885 16 57702099 57723975 +
CCDC135 ENSG00000159625 16 57728705 57765717 +
KATNB1 ENSG00000140854 16 57769642 57791162 +
KIFC3 ENSG00000140859 16 57792129 57896957 -
CTD-2600O9.1 ENSG00000187185 16 57832098 57850850 +
CNGB1 ENSG00000070729 16 57917503 58005020 -
TEPP ENSG00000159648 16 58010339 58022020 +
ZNF319 ENSG00000166188 16 58028572 58034357 -
USB1 ENSG00000103005 16 58033450 58055522 +
MMP15 ENSG00000102996 16 58059470 58080805 +
C16orf80 ENSG00000070761 16 58147496 58163354 -
CSNK2A2 ENSG00000070770 16 58191811 58231824 -
CCDC113 ENSG00000103021 16 58265061 58317740 +
PRSS54 ENSG00000103023 16 58313901 58328951 -
GINS3 ENSG00000181938 16 58328984 58440048 +
NDRG4 ENSG00000103034 16 58496750 58547532 +
SETD6 ENSG00000103037 16 58549383 58554431 +
CNO 1 ENSG00000125107 16 58553855 58663790 -
SLC38A7 ENSG00000103042 16 58699013 58719008 -
GOT2 ENSG00000125166 16 58741035 58768261 -
RP11-105C20.2 ENSG00000260240 16 59743897 59788752 -
CDH8 ENSG00000150394 16 61681146 62070939 -
CDH11 ENSG00000140937 16 64977656 65160015 -
Gene symbol Ensembl ID Chromosome Start End Strand
CDH5 ENSG00000179776 16 66400533 66438686 +
BEAN1 ENSG00000166546 16 66461200 66527432 +
RP11-403P17.5 ENSG00000260851 16 66503715 66551215 -
AC132186.1 ENSG00000247270 16 66516775 66519747 -
TK2 ENSG00000166548 16 66541906 66586447 -
CKLF ENSG00000217555 16 66586466 66600331 +
CKLF-CMTM1 ENSG00000254788 16 66586490 66613038 +
CMTM1 ENSG00000089505 16 66600294 66613040 +
CMTM2 ENSG00000140932 16 66613351 66622178 +
CMTM3 ENSG00000140931 16 66637777 66647795 +
CMTM4 ENSG00000183723 16 66648653 66730610 -
DYNC1LI2 ENSG00000135720 16 66754796 66785701 -
CCDC79 ENSG00000249961 16 66788879 66835523 -
NAE1 ENSG00000159593 16 66836778 66907159 -
CA7 ENSG00000168748 16 66878282 66888056 +
PDP2 ENSG00000172840 16 66912492 66929657 +
CDH16 ENSG00000166589 16 66942025 66952887 -
RRAD ENSG00000166592 16 66955582 66959547 -
FAM96B ENSG00000166595 16 66965959 66968326 -
CES2 ENSG00000172831 16 66968347 66978999 +
CES3 ENSG00000172828 16 66995140 67009051 +
CES4A ENSG00000172824 16 67022492 67043661 +
CBFB ENSG00000067955 16 67063019 67134961 +
C16orf70 ENSG00000125149 16 67143861 67182442 +
B3GN 9 ENSG00000237172 16 67182008 67185117 -
TRADD ENSG00000102871 16 67188083 67194201 -
FBXL8 ENSG00000135722 16 67193834 67199718 +
RP11-5A19.5 ENSG00000265690 16 67197288 67199711 +
HSF4 ENSG00000102878 16 67197288 67203848 +
NOL3 ENSG00000140939 16 67204057 67209643 +
KIAA0895L ENSG00000196123 16 67209505 67217943 -
EXOC3L1 ENSG00000179044 16 67218269 67224107 -
E2F4 ENSG00000205250 16 67226072 67232821 +
ELMO3 ENSG00000102890 16 67233014 67237932 +
LRRC29 ENSG00000125122 16 67241042 67260951 -
AC040160.1 ENSG00000237102 16 67244251 67260930 -
TMEM208 ENSG00000168701 16 67261006 67263181 +
FHOD1 ENSG00000135723 16 67263290 67281561 -
Gene symbol Ensembl ID Chromosome Start End Strand
SLC9A5 ENSG00000135740 16 67271586 67306093 +
PLEKHG4 ENSG00000196155 16 67311413 67323402 +
KCTD19 ENSG00000168676 16 67323331 67360666 -
LRRC36 ENSG00000159708 16 67360701 67419106 +
TPPP3 ENSG00000159713 16 67423712 67427438 -
ZDHHC1 ENSG00000159714 16 67428322 67450736 -
HSD11B2 ENSG00000176387 16 67464555 67471456 +
ATP6V0D1 ENSG00000159720 16 67471917 67515140 -
AGRP ENSG00000159723 16 67516474 67517716 -
FAM65A ENSG00000039523 16 67552321 67580689 +
CTCF ENSG00000102974 16 67596310 67673086 +
RLTPR ENSG00000159753 16 67679030 67691456 +
ACD ENSG00000102977 16 67691433 67694713 -
PARD6A ENSG00000102981 16 67694851 67696680 +
ENKD1 ENSG00000124074 16 67696848 67700667 -
C16orf86 ENSG00000159761 16 67700719 67702660 +
GFOD2 ENSG00000141098 16 67708436 67753324 -
RANBPIO ENSG00000141084 16 67757005 67840555 -
TSNAXIP1 ENSG00000102904 16 67840668 67866051 +
CENPT ENSG00000102901 16 67862060 67881714 -
THAP11 ENSG00000168286 16 67876213 67878097 +
NUTF2 ENSG00000102898 16 67880635 67906470 +
EDC4 ENSG00000038358 16 67906926 67918406 +
NRN1L ENSG00000188038 16 67918708 67922758 +
PSKH1 ENSG00000159792 16 67927175 67963860 +
CTRL ENSG00000141086 16 67961543 67966317 -
CTC-479C5.12 ENSG00000261884 16 67963517 67969920 -
PSMB10 ENSG00000205220 16 67968405 67970990 -
LCAT ENSG00000213398 16 67973653 67978034 -
SLC12A4 ENSG00000124067 16 67977377 68003504 -
DPEP3 ENSG00000141096 16 68009566 68014732 -
DPEP2 ENSG00000167261 16 68021297 68034489 -
DUS2L ENSG00000167264 16 68021649 68113223 +
DDX28 ENSG00000182810 16 68055179 68057770 -
NFATC3 ENSG00000072736 16 68118654 68263162 +
ESRP2 ENSG00000103067 16 68263014 68272005 -
PLA2G15 ENSG00000103066 16 68279207 68294961 +
SLC7A6 ENSG00000103064 16 68298433 68335722 +
Gene symbol Ensembl ID Chromosome Start End Strand
SLC7A60S ENSG00000103061 16 68318406 68344849 -
PRM 7 ENSG00000132600 16 68344877 68392466 +
SMPD3 ENSG00000103056 16 68392231 68482591 -
ZFP90 ENSG00000184939 16 68563993 68609948 +
CDH3 ENSG00000062038 16 68670092 68756519 +
CDH1 ENSG00000039068 16 68771128 68869445 +
TMC07 ENSG00000103047 16 68877507 69119083 +
HAS3 ENSG00000103044 16 69139467 69152622 +
CHTF8 ENSG00000168802 16 69151913 69166487 -
CHTF8 ENSG00000263203 16 69152757 69154331 -
CIRH1A ENSG00000141076 16 69165194 69202941 +
SNTB2 ENSG00000168807 16 69221032 69342955 +
VPS4A ENSG00000132612 16 69333562 69358949 +
RP11-343C2.3 ENSG00000260914 16 69333585 69354614 +
COG8 ENSG00000213380 16 69354043 69373570 -
PDF ENSG00000258429 16 69362524 69364498 -
RP11-343C2.8 ENSG00000261576 16 69362547 69368774 -
COG8 ENSG00000260371 16 69368994 69390209 -
RP11-343C2.7 ENSG00000259900 16 69369179 69385633 -
NIP7 ENSG00000132603 16 69373333 69377014 +
TMED6 ENSG00000157315 16 69377151 69385712 -
TERF2 ENSG00000132604 16 69389464 69442474 -
CYB5B ENSG00000103018 16 69458428 69500169 +
ZFHX3 ENSG00000140836 16 72816784 73093597 -
C16orf47 ENSG00000197445 16 73160536 73178346 -
RFWD3 ENSG00000168411 16 74655292 74700779 -
MLKL ENSG00000168404 16 74705753 74734858 -
FA2H ENSG00000103089 16 74746853 74808729 -
WDR59 ENSG00000103091 16 74907468 75034071 -
ZNRF1 ENSG00000186187 16 75032928 75144892 +
LDHD ENSG00000166816 16 75145758 75150669 -
ZFP1 ENSG00000184517 16 75182390 75206134 +
CTRB2 ENSG00000168928 16 75237994 75241083 -
CTRB1 ENSG00000168925 16 75252898 75258822 +
BCAR1 ENSG00000050820 16 75262928 75301951 -
CFDP1 ENSG00000153774 16 75327596 75467383 -
RP11-77K12.1 ENSG00000261717 16 75446582 75498604 -
TMEM170A ENSG00000166822 16 75476952 75499395 -
Gene symbol Ensembl ID Chromosome Start End Strand
CHST6 ENSG00000183196 16 75510949 75529282 -
RP11-77K12.7 ENSG00000260092 16 75562430 75579326 -
CHST5 ENSG00000135702 16 75562433 75569145 -
TMEM231 ENSG00000205084 16 75572015 75590176 -
GABARAPL2 ENSG00000034713 16 75600249 75611779 +
ADA 1 ENSG00000065457 16 75630879 75657198 -
KARS ENSG00000065427 16 75661622 75682541 -
TERF2IP ENSG00000166848 16 75681684 75795051 +
AC025287.1 ENSG00000214325 16 75728367 75734089 -
CNTNAP4 ENSG00000152910 16 76311176 76593135 +
RP11-58C22.1 ENSG00000261833 16 76587314 76669520 +
MON1B ENSG00000103111 16 77224732 77236302 +
SYCE1L ENSG00000205078 16 77233294 77247112 +
ADAMTS18 ENSG00000140873 16 77281710 77469011 -
NUDT7 ENSG00000140876 16 77756411 77776157 +
VA 1L ENSG00000171724 16 77822427 78014004 +
CLEC3A ENSG00000166509 16 78056412 78100658 +
WWOX ENSG00000186153 16 78133310 79246564 +
PIH1 ENSG00000268977 16 79015647 79015739 -
MAF ENSG00000178573 16 79619740 79634611 -
DYNLRB2 ENSG00000168589 16 80574631 80584657 +
CDYL2 ENSG00000166446 16 80637609 80838226 -
CMC2 ENSG00000103121 16 81009698 81053875 -
CENPN ENSG00000166451 16 81040103 81066719 +
ATMIN ENSG00000166454 16 81069452 81080963 +
C16orf46 ENSG00000166455 16 81087102 81110872 -
GCSH ENSG00000140905 16 81115566 81130008 -
PKD1L2 ENSG00000269323 16 81204345 81253975 -
BCMOl ENSG00000135697 16 81272053 81324747 +
GAN ENSG00000127688 16 81348557 81413940 +
CMIP ENSG00000153815 16 81478775 81745173 +
PLCG2 ENSG00000197943 16 81772702 81991899 +
SDR42E1 ENSG00000184860 16 82031257 82045093 -
HSD17B2 ENSG00000086696 16 82068609 82132139 +
MPHOSPH6 ENSG00000135698 16 82181403 82203831 -
CDH13 ENSG00000140945 16 82660408 83830204 +
HSBP1 ENSG00000230989 16 83841448 83853342 +
MLYCD ENSG00000103150 16 83932731 83949787 +
Gene symbol Ensembl ID Chromosome Start End Strand
0SGIN1 ENSG00000140961 16 83981887 83999937 +
NECAB2 ENSG00000103154 16 84002237 84036381 +
SLC38A8 ENSG00000166558 16 84043272 84076241 -
MBTPS1 ENSG00000140943 16 84087368 84150511 -
HSDL1 ENSG00000103160 16 84155886 84178797 -
DNAAF1 ENSG00000154099 16 84178865 84212373 +
TAF1C ENSG00000103168 16 84211458 84220669 -
ADAD2 ENSG00000140955 16 84224744 84230774 +
KCNG4 ENSG00000168418 16 84255823 84273356 -
WFDC1 ENSG00000103175 16 84328252 84363450 +
ATP2C2 ENSG00000064270 16 84402133 84497793 +
KIAA1609 ENSG00000140950 16 84511681 84587639 -
COTL1 ENSG00000103187 16 84599200 84651683 -
KLHL36 ENSG00000135686 16 84682131 84701292 +
USP10 ENSG00000103194 16 84733584 84813528 +
CRISPLD2 ENSG00000103196 16 84853590 84954374 +
ZDHHC7 ENSG00000153786 16 85007787 85045141 -
KIAA0513 ENSG00000135709 16 85061375 85127836 +
FAM92B ENSG00000153789 16 85131965 85146114 -
RP11-680G10.1 ENSG00000261567 16 85391069 85393055 +
GSE1 ENSG00000131149 16 85645015 85709810 +
GINS2 ENSG00000131153 16 85709804 85723679 -
C16orf74 ENSG00000154102 16 85741123 85784689 -
EMC8 ENSG00000131148 16 85805364 85833214 -
COX4I1 ENSG00000131143 16 85832239 85840650 +
IRF8 ENSG00000140968 16 85932409 85956197 +
FOXF1 ENSG00000103241 16 86544133 86548076 +
MTHFSD ENSG00000103248 16 86563782 86588841 -
FOXC2 ENSG00000176692 16 86600857 86602539 +
FOXL1 ENSG00000176678 16 86609974 86615303 +
C16orf95 ENSG00000260456 16 87117168 87351022 -
RP11-178L8.4 ENSG00000131152 16 87336482 87367879 -
FBX031 ENSG00000103264 16 87360593 87425748 -
MAP1LC3B ENSG00000140941 16 87417601 87438385 +
ZCCHC14 ENSG00000140948 16 87439852 87525651 -
JPH3 ENSG00000154118 16 87635441 87731762 +
AC010536.1 ENSG00000226180 16 87727144 87729753 -
FLJ00104 ENSG00000205047 16 87731749 87739290 -
Gene symbol Ensembl ID Chromosome Start End Strand
SEGMENT-2
METTL4 ENSG00000101574 18 2537524 2571508 -
NDC80 ENSG00000080986 18 2571510 2616634 +
SMCHD1 ENSG00000101596 18 2655737 2805015 +
EMILIN2 ENSG00000132205 18 2847028 2915991 +
LPIN2 ENSG00000101577 18 2916992 3013313 -
MYOM1 ENSG00000101605 18 3066805 3220106 -
MYL12A ENSG00000101608 18 3247479 3256234 +
MYL12B ENSG00000118680 18 3261907 3278282 +
TGIF1 ENSG00000177426 18 3411606 3459976 +
DLGAP1 ENSG00000170579 18 3496030 4455335 -
C18orf42 ENSG00000231824 18 5145284 5197502 -
ZFP161 ENSG00000198081 18 5289018 5297052 -
EPB41L3 ENSG00000082397 18 5392383 5630699 -
TMEM200C ENSG00000206432 18 5889419 5895954 -
L3MBTL4 ENSG00000154655 18 5954705 6415236 -
RP11-865B13.1 ENSG00000265944 18 6511415 6590652 +
ARHGAP28 ENSG00000088756 18 6729717 6915715 +
LAMA1 ENSG00000101680 18 6941743 7117813 -
LRRC30 ENSG00000206422 18 7231123 7232045 +
PTPRM ENSG00000173482 18 7566780 8406859 +
AP001094.1 ENSG00000268046 18 8336437 8337038 -
RAB12 ENSG00000206418 18 8609443 8639379 +
SOGA2 ENSG00000168502 18 8705659 8832776 +
NDUFV2 ENSG00000178127 18 9102628 9134343 +
ANKRD12 ENSG00000101745 18 9136226 9285206 +
TWSG1 ENSG00000128791 18 9334765 9402418 +
RALBPl ENSG00000017797 18 9475007 9538114 +
PPP4R1 ENSG00000154845 18 9546789 9615238 -
RAB31 ENSG00000168461 18 9708162 9862553 +
TXNDC2 ENSG00000168454 18 9885763 9889272 +
VAPA ENSG00000101558 18 9913999 9960018 +
APCDD1 ENSG00000154856 18 10454625 10488698 +
NAPG ENSG00000134265 18 10525902 10552758 +
PIEZ02 ENSG00000154864 18 10666480 11148587 -
GNAL ENSG00000141404 18 11688955 11885684 +
CHMP1B ENSG00000255112 18 11851395 11854448 +
MPPE1 ENSG00000154889 18 11882621 11909222 -
IMPA2 ENSG00000141401 18 11981024 12030876 +
SLMOl ENSG00000141391 18 12407895 12432237 +
SPIRE1 ENSG00000134278 18 12446511 12658133 -
AP005482.1 ENSG00000215527 18 12658042 12658892 +
CEP76 ENSG00000101624 18 12661832 12702776 -
Gene symbol Ensembl ID Chromosome Start End Strand
PSMG2 ENSG00000128789 18 12702425 12725739 +
PTPN2 ENSG00000175354 18 12785477 12929642 -
SEH1L ENSG00000085415 18 12947132 12987535 +
CEP192 ENSG00000101639 18 12991361 13125051 +
LDLRAD4 ENSG00000168675 18 13217497 13652754 +
FAM21 OA ENSG00000177150 18 13663346 13726662 -
RNMT ENSG00000101654 18 13726659 13764557 +
MC5R ENSG00000176136 18 13824154 13826861 +
ESCOl ENSG00000141446 18 19109242 19180845 -
SNRPD1 ENSG00000167088 18 19192228 19210344 +
ABHD3 ENSG00000158201 18 19230858 19284766 -
MIB1 ENSG00000101752 18 19284918 19450918 +
RP11-595B24.2 ENSG00000263588 18 19668021 19678741 +
GATA6 ENSG00000141448 18 19749404 19782491 +
CTAGE1 ENSG00000255212 18 19993564 19994830 -
CTAGE1 ENSG00000212710 18 19993573 19997878 -
RBBP8 ENSG00000101773 18 20378224 20606451 +
CABLESI ENSG00000134508 18 20714528 20840431 +
TMEM241 ENSG00000134490 18 20777108 21017925 -
RIOK3 ENSG00000101782 18 21032787 21066567 +
C18orf8 ENSG00000141452 18 21083473 21111746 +
NPC1 ENSG00000141458 18 21086307 21166862 -
ANKRD29 ENSG00000154065 18 21178890 21242849 -
LAMA3 ENSG00000053747 18 21269407 21535030 +
TTC39C ENSG00000168234 18 21572737 21715574 +
CABYR ENSG00000154040 18 21718942 21741567 +
OSBPL1A ENSG00000141447 18 21742008 21977844 -
IMPACT ENSG00000154059 18 22006580 22033499 +
HRH4 ENSG00000134489 18 22040593 22059921 +
ZNF521 ENSG00000198795 18 22641890 22932154 -
SS18 ENSG00000141380 18 23596578 23671181 -
PSMA8 ENSG00000154611 18 23713816 23773319 +
TAF4B ENSG00000141384 18 23805900 23971649 +
KCTD1 ENSG00000134504 18 24034874 24237365 -
AQP4 ENSG00000171885 18 24432002 24445782 -
CHST9 ENSG00000154080 18 24495595 24765281 -
CDH2 ENSG00000170558 18 25530930 25757410 -
DSC3 ENSG00000134762 18 28569974 28622781 -
DSC2 ENSG00000134755 18 28645940 28682378 -
DSC1 ENSG00000134765 18 28709199 28742819 -
DSG1 ENSG00000134760 18 28898052 28936992 +
DSG4 ENSG00000175065 18 28956740 28994875 +
DSG3 ENSG00000134757 18 29027758 29058665 +
Gene symbol Ensembl ID Chromosome Start End Strand
DSG2 ENSG00000046604 18 29078006 29128971 +
TTR ENSG00000118271 18 29171689 29178974 +
B4GALT6 ENSG00000118276 18 29202210 29265799 -
SLC25A52 ENSG00000141437 18 29339525 29340843 -
TRAPPC8 ENSG00000153339 18 29409136 29533099 -
RNF125 ENSG00000101695 18 29598335 29653176 +
RNF138 ENSG00000134758 18 29671818 29711524 +
FAM59A ENSG00000141441 18 29704840 30050447 -
MEP1B ENSG00000141434 18 29765032 29800367 +
KLHL14 ENSG00000197705 18 30252634 30353025 -
AC012123.1 ENSG00000228835 18 30349758 30354376 +
CCDC178 ENSG00000166960 18 30517366 31021065 -
ASXL3 ENSG00000141431 18 31158579 31331156 +
NOL4 ENSG00000101746 18 31431064 31804916 -
DTNA ENSG00000134769 18 32073254 32471808 +
MAPRE2 ENSG00000166974 18 32556892 32723434 +
ZNF397 ENSG00000186812 18 32820994 32847097 +
ZSCAN30 ENSG00000186814 18 32831032 32870196 -
ZNF24 ENSG00000172466 18 32912176 32925446 -
ZNF396 ENSG00000186496 18 32946661 32957301 -
RP11-322E11.6 ENSG00000267140 18 33023835 33077904 -
INO80C ENSG00000153391 18 33032194 33077955 -
GALN 1 ENSG00000141429 18 33161003 33291798 +
C18orf21 ENSG00000141428 18 33552046 33559241 +
RPRD1A ENSG00000141425 18 33564350 33647539 -
SLC39A6 ENSG00000141424 18 33688495 33709348 -
ELP2 ENSG00000134759 18 33709407 33757909 +
MOCOS ENSG00000075643 18 33767482 33852120 +
FHOD3 ENSG00000134775 18 33877680 34360018 +
TPGS2 ENSG00000134779 18 34359987 34409158 -
KIAA1328 ENSG00000150477 18 34409069 34812101 +
CELF4 ENSG00000101489 18 34823010 35146000 -
PIK3C3 ENSG00000078142 18 39535171 39667794 +
RIT2 ENSG00000152214 18 40323192 40695657 -
SYT4 ENSG00000132872 18 40847859 40857615 -
SETBP1 ENSG00000152217 18 42260138 42648475 +
SLC14A2 ENSG00000132874 18 42792960 43263072 +
SLC14A1 ENSG00000141469 18 43304092 43332485 +
SIGLEC15 ENSG00000197046 18 43405477 43424045 +
EPG5 ENSG00000152223 18 43427574 43547240 -
PSTPIP2 ENSG00000152229 18 43563502 43652238 -
ATP5A1 ENSG00000152234 18 43664110 43684300 -
HAUS1 ENSG00000152240 18 43684298 43708299 +
Gene symbol Ensembl ID Chromosome Start End Strand
C18orf25 ENSG00000152242 18 43753519 43846949 +
RNF165 ENSG00000141622 18 43906772 44043103 +
L0XHD1 ENSG00000167210 18 44056935 44236996 -
ST8SIA5 ENSG00000101638 18 44259081 44339220 -
PIAS2 ENSG00000078043 18 44388353 44500123 -
KATNAL2 ENSG00000167216 18 44497455 44627658 +
TCEB3CL2 ENSG00000266996 18 44542731 44544607 -
TCEB3CL ENSG00000234298 18 44548658 44550534 -
TCEB3C ENSG00000183791 18 44554573 44556449 -
TCEB3B ENSG00000206181 18 44558943 44561988 -
HDHD2 ENSG00000167220 18 44633774 44676871 -
IER3IP1 ENSG00000267228 18 44661027 44702652 -
IER3IP1 ENSG00000134049 18 44681413 44702745 -
SKOR2 ENSG00000215474 18 44746293 44775554 -
SMAD2 ENSG00000175387 18 45357922 45457515 -
ZBTB7C ENSG00000184828 18 45553044 45937123 -
AC091150.1 ENSG00000268960 18 45778672 45779208 +
CTIF ENSG00000134030 18 46065417 46389588 +
SMAD7 ENSG00000101665 18 46446223 46477081 -
DYM ENSG00000141627 18 46570039 46987717 -
C18orf32 ENSG00000177576 18 47008028 47013622 -
RPL17- ENSG00000215472 18 47008051 47018906
C180RF32
RPL17 ENSG00000265681 18 47014851 47018893
LIPG ENSG00000101670 18 47087069 47119276
ACAA2 ENSG00000167315 18 47309869 47340323 -
RP11-886H22.1 ENSG00000266997 18 47322169 47363972 -
MY05B ENSG00000167306 18 47349183 47721463 -
CCDC11 ENSG00000172361 18 47753563 47792892 -
MBD1 ENSG00000141644 18 47793252 47808144 -
CXXC1 ENSG00000154832 18 47808713 47814674 -
SKA1 ENSG00000154839 18 47901365 47920543 +
MAPK4 ENSG00000141639 18 48086448 48258194 +
MRO ENSG00000134042 18 48321491 48351772 -
ME2 ENSG00000082212 18 48405419 48474691 +
ELAC1 ENSG00000141642 18 48494361 48514491 +
RP11-729L2.2 ENSG00000267699 18 48494393 48584514 +
SMAD4 ENSG00000141646 18 48494410 48611415 +
MEX3C ENSG00000176624 18 48700920 48744674 -
DCC ENSG00000187323 18 49866542 51057784 +
MBD2 ENSG00000134046 18 51679079 51751158 -
POLI ENSG00000101751 18 51795774 51847636 +
STARD6 ENSG00000174448 18 51850964 51884334 -
C18orf54 ENSG00000166845 18 51884287 51911588 +
Gene symbol Ensembl ID Chromosome Start End Strand
DYNAP ENSG00000178690 18 52254988 52266724 +
RAB27B ENSG00000041353 18 52385091 52562747 +
CCDC68 ENSG00000166510 18 52568740 52626739 -
TCF4 ENSG00000196628 18 52889562 53332018 -
TXNL1 ENSG00000091164 18 54264439 54318831 -
WDR7 ENSG00000091157 18 54318574 54698828 +
BOD1L2 ENSG00000228075 18 54814293 54817531 +
ST8SIA3 ENSG00000177511 18 55018044 55038962 +
ONECUT2 ENSG00000119547 18 55102917 55158530 +
FECH ENSG00000066926 18 55215515 55254004 -
NARS ENSG00000134440 18 55267888 55289445 -
ATP8B1 ENSG00000081923 18 55313658 55470333 -
NEDD4L ENSG00000049759 18 55711599 56068772 +
ALPK2 ENSG00000198796 18 56148479 56296189 -
MAL 1 ENSG00000172175 18 56338618 56417371 +
ZNF532 ENSG00000074657 18 56529832 56653712 +
SEC11C ENSG00000166562 18 56806709 56826068 +
GRP ENSG00000134443 18 56887400 56898006 +
RAX ENSG00000134438 18 56934267 56941318 -
CPLX4 ENSG00000166569 18 56942388 56985881 -
LMAN1 ENSG00000074695 18 56995055 57027194 -
CCBE1 ENSG00000183287 18 57101149 57364612 -
PMAIP1 ENSG00000141682 18 57567180 57571538 +
MC4R ENSG00000166603 18 58038564 58040001 -
CDH20 ENSG00000101542 18 59000815 59223006 +
RNF152 ENSG00000176641 18 59475296 59561480 -
PIGN ENSG00000197563 18 59710800 59854351 -
KIAA1468 ENSG00000134444 18 59854491 59974355 +
TNFRSF11A ENSG00000141655 18 59992520 60058516 +
ZCCHC2 ENSG00000141664 18 60190240 60254942 +
PHLPP1 ENSG00000081913 18 60382672 60647666 +
AC015989.1 ENSG00000215431 18 60491423 60492724 +
AC015989.2 ENSG00000269630 18 60505640 60505948 -
BCL2 ENSG00000171791 18 60790579 60987361 -
KDSR ENSG00000119537 18 60994971 61034743 -
VPS4B ENSG00000119541 18 61056423 61089716 -
SERPINB5 ENSG00000206075 18 61143994 61172318 +
SERPINB12 ENSG00000166634 18 61223393 61234244 +
SERPINB13 ENSG00000197641 18 61254223 61271873 +
SERPINB4 ENSG00000206073 18 61304493 61311532 -
SERPINB3 ENSG00000057149 18 61322431 61329197 -
SERPINB7 ENSG00000166396 18 61420169 61472604 +
SERPINB2 ENSG00000197632 18 61538926 61571124 +
Gene symbol Ensembl ID Chromosome Start End Strand
SERPINB10 ENSG00000242550 18 61564408 61603345 +
AC009802.1 ENSG00000268706 18 61602042 61609601 -
HMSD ENSG00000221887 18 61616535 61649008 +
SERPINB8 ENSG00000166401 18 61637159 61672278 +
CDH7 ENSG00000081138 18 63417488 63548638 +
CDH19 ENSG00000071991 18 64168320 64271375 -
DSEL ENSG00000171451 18 65173819 65184217 -
TMX3 ENSG00000166479 18 66340925 66382535 -
CCDC102B ENSG00000150636 18 66382446 66722426 +
RP11-861L17.3 ENSG00000264472 18 66567018 66569492 -
DOK6 ENSG00000206052 18 67068291 67516323 +
CD226 ENSG00000150637 18 67498394 67629039 -
RTTN ENSG00000176225 18 67671029 67873181 -
SOCS6 ENSG00000170677 18 67956137 67997436 +
RP11-4104.1 ENSG00000266258 18 68002675 68019695 +
RP11-433A23.1 ENSG00000263417 18 68297755 68317980 -
RP11-723G8.2 ENSG00000265352 18 69399851 69455364 -
CBLN2 ENSG00000141668 18 70203915 70305756 -
NETOl ENSG00000166342 18 70409549 70535381 -
RP11-169F17.1 ENSG00000263711 18 70818476 70931715 -
FBX015 ENSG00000141665 18 71740588 71815100 -
TIMM21 ENSG00000075336 18 71815746 71826197 +
CYB5A ENSG00000166347 18 71920530 71959251 -
C18orf63 ENSG00000206043 18 71983048 72026422 +
FAM69C ENSG00000187773 18 72102963 72125179 -
CNDP2 ENSG00000133313 18 72163051 72188366 +
CNDP1 ENSG00000150656 18 72201675 72254448 +
ZNF407 ENSG00000215421 18 72265106 72777627 +
ZADH2 ENSG00000180011 18 72907063 72921303 -
TSHZ1 ENSG00000179981 18 72922710 73001905 +
RP11-321M21.3 ENSG00000264116 18 73118967 73130995 +
C18orf62 ENSG00000206026 18 73121431 73139658 -
RP11-94B19.4 ENSG00000266614 18 73971121 73972069 +
ZNF516 ENSG00000101493 18 74069644 74207146 -
RP11-17M16.1 ENSG00000220032 18 74207477 74210045 +
RP11-111H3.1 ENSG00000263812 18 74240612 74322925 +
RP11-162A12.2 ENSG00000264278 18 74506688 74534251 -
ZNF236 ENSG00000130856 18 74534563 74682683 +
MBP ENSG00000197971 18 74690783 74845639 -
GALR1 ENSG00000166573 18 74962505 74980858 +
SALL3 ENSG00000256463 18 76740275 76762677 +
SEGMENT-3
LA S2 ENSG00000150457 13 21547171 21635718 -
Gene symbol Ensembl ID Chromosome Start End Strand
SAP18 ENSG00000150459 13 21714653 21723221 +
SKA3 ENSG00000165480 13 21727734 21750741 -
MRP63 ENSG00000173141 13 21750784 21753223 +
ZDHHC20 ENSG00000215570 13 21946717 21949350 -
ZDHHC20 ENSG00000180776 13 21950263 22033509 -
EFHA1 ENSG00000165487 13 22066836 22178353 -
FGF9 ENSG00000102678 13 22245522 22278637 +
SGCG ENSG00000102683 13 23755091 23899304 +
SACS ENSG00000151835 13 23902965 24007841 -
TNFRSF19 ENSG00000127863 13 24144509 24250232 +
MIPEP ENSG00000027001 13 24304328 24463558 -
AL139080.1 ENSG00000268735 13 24322243 24323901 +
C1QTNF9B ENSG00000205863 13 24465238 24476794 -
SPATA13 ENSG00000182957 13 24734861 24896096 +
C1QTNF9 ENSG00000240654 13 24881304 24896673 +
C1QTNF9B-AS1 ENSG00000205850 13 24895264 24895566 -
PARP4 ENSG00000102699 13 24995064 25086948 -
ATP12A ENSG00000075673 13 25254549 25285921 +
RNF17 ENSG00000132972 13 25338290 25454059 +
CENPJ ENSG00000151849 13 25457171 25497018 -
LSP1 ENSG00000269099 13 25591541 25591675 +
PABPC3 ENSG00000151846 13 25670006 25673392 +
FAM123A ENSG00000165566 13 25735822 25746426 -
MTMR6 ENSG00000139505 13 25802307 25862147 -
NUPL1 ENSG00000139496 13 25875662 25923938 +
A P8A2 ENSG00000132932 13 25946209 26599989 +
AL138815.1 ENSG00000215549 13 26442061 26455095 +
AL138815.2 ENSG00000268344 13 26452422 26452679 -
SHISA2 ENSG00000180730 13 26618735 26625198 -
RNF6 ENSG00000127870 13 26706253 26796791 -
CDK8 ENSG00000132964 13 26828276 26979375 +
WASF3 ENSG00000132970 13 27131840 27263085 +
GPR12 ENSG00000132975 13 27329341 27334922 -
USP12 ENSG00000152484 13 27640293 27746033 -
RPL21 ENSG00000122026 13 27825446 27830828 +
RASLllA ENSG00000122035 13 27844464 27847827 +
GTF3A ENSG00000122034 13 27998681 28009958 +
M IF3 ENSG00000122033 13 28009776 28024739 -
LNX2 ENSG00000139517 13 28120050 28194541 -
POLR1D ENSG00000186184 13 28194903 28241548 +
GSX1 ENSG00000169840 13 28366780 28368905 +
PDX1 ENSG00000139515 13 28494157 28500368 +
ATP5EP2 ENSG00000180389 13 28519343 28519727 +
Gene symbol Ensembl ID Chromosome Start End Strand
CDX2 ENSG00000165556 13 28535826 28545276 -
PRHOXNB ENSG00000183463 13 28552243 28562774 -
FLT3 ENSG00000122025 13 28577411 28674729 -
PAN3 ENSG00000152520 13 28712643 28869475 +
FLT1 ENSG00000102755 13 28874489 29069265 -
POMP ENSG00000132963 13 29233241 29253062 +
SLC46A3 ENSG00000139508 13 29274201 29293107 -
MTUS2 ENSG00000132938 13 29598748 30077892 +
SLC7A1 ENSG00000139514 13 30083547 30169825 -
UBL3 ENSG00000122042 13 30338508 30424821 -
LINC00544 ENSG00000122043 13 30510042 30524625 +
KATNAL1 ENSG00000102781 13 30776767 30881621 -
HMGB1 ENSG00000189403 13 31032884 31191734 -
USPL1 ENSG00000132952 13 31191830 31233686 +
ALOX5AP ENSG00000132965 13 31309645 31338556 +
MEDAG ENSG00000102802 13 31480328 31499709 +
TEX26 ENSG00000175664 13 31506840 31549639 +
HSPH1 ENSG00000120694 13 31710762 31736525 -
B3GALTL ENSG00000187676 13 31774073 31906413 +
RXFP2 ENSG00000133105 13 32313674 32377009 +
FRY ENSG00000073910 13 32605437 32870794 +
ZAR1L ENSG00000189167 13 32877837 32889481 -
BRCA2 ENSG00000139618 13 32889611 32973805 +
N4BP2L1 ENSG00000139597 13 32974861 33007091 -
RP11-298P3.4 ENSG00000139617 13 33006554 33054775 -
N4BP2L2 ENSG00000244754 13 33006924 33112970 -
PDS5B ENSG00000083642 13 33160564 33352157 +
KL ENSG00000133116 13 33590207 33640282 +
STARD13 ENSG00000133121 13 33677307 33924767 -
RFC3 ENSG00000133119 13 34392186 34540695 +
NBEA ENSG00000172915 13 35516424 36247159 +
MAB21L1 ENSG00000180660 13 36047926 36050832 -
DCLK1 ENSG00000133083 13 36345478 36705443 -
SOHLH2 ENSG00000120669 13 36742345 36871979 -
CCDC169- ENSG00000250709 13 36742931 36871979 — SOHLH2
CCDC169 ENSG00000242715 13 36801182 36871977 -
SPG20 ENSG00000133104 13 36875775 36944317 -
SPG20OS ENSG00000120664 13 36920568 36943738 +
CCNA1 ENSG00000133101 13 37005967 37017019 +
SERTM1 ENSG00000180440 13 37248049 37271976 +
RFXAP ENSG00000133111 13 37393361 37403241 +
DLEU1 ENSG00000176124 13 50656307 51298199 +
DLEU7 ENSG00000186047 13 51285144 51418075 -
Gene symbol Ensembl ID Chromosome Start End Strand
RNASEH2B ENSG00000136104 13 51483814 51544592 +
FAM124A ENSG00000150510 13 51796503 51857930 +
SERPINE3 ENSG00000253309 13 51909909 51938871 +
INTS6 ENSG00000102786 13 51928213 52028400 -
WDFY2 ENSG00000139668 13 52158644 52334135 +
DHRS12 ENSG00000102796 13 52342129 52378293 -
CCDC70 ENSG00000123171 13 52436117 52440366 +
ATP7B ENSG00000123191 13 52506809 52585630 -
ALG11 ENSG00000253710 13 52586534 52603800 +
UTP14C ENSG00000253797 13 52598827 52607701 +
LECT1 ENSG00000136110 13 53277399 53313947 -
PCDH8 ENSG00000136099 13 53418109 53422775 -
OLFM4 ENSG00000102837 13 53602830 53626196 +
PRR2 OA ENSG00000204919 13 57715052 57718073 +
PRR20B ENSG00000204918 13 57721622 57724643 +
PRR20C ENSG00000229665 13 57728326 57730513 +
PRR20D ENSG00000227151 13 57734897 57737084 +
PRR20E ENSG00000234278 13 57741331 57744352 +
PCDH17 ENSG00000118946 13 58205944 58303445 +
DIAPH3 ENSG00000139734 13 60239717 60738119 -
TDRD3 ENSG00000083544 13 60970591 61148012 +
SEGMENT-4
RSF1 ENSG00000048649 11 77371041 77532063 -
AAMDC ENSG00000087884 11 77532155 77629478 +
INTS4 ENSG00000149262 11 77589766 77705724 -
KCTD14 ENSG00000151364 11 77726761 77757237 -
NDUFC2-KCTD14 ENSG00000259112 11 77728017 77790911 -
THRSP ENSG00000151365 11 77774907 77779397 +
NDUFC2 ENSG00000151366 11 77779350 77791265 -
ALG8 ENSG00000159063 11 77811982 77850706 -
KCTD21 ENSG00000188997 11 77882295 77899868 -
USP35 ENSG00000118369 11 77899858 77925757 +
GAB2 ENSG00000033327 11 77926343 78129394 -
NARS2 ENSG00000137513 11 78147007 78285919 -
TENM4 ENSG00000149256 11 78363876 79151992 -
FAM181B ENSG00000182103 11 82443053 82444906 -
PRCP ENSG00000137509 11 82534544 82681626 -
Cllorf82 ENSG00000165490 11 82611017 82669319 +
RAB30 ENSG00000137502 11 82684175 82782965 -
PCF11 ENSG00000165494 11 82868030 82898493 +
ANKRD42 ENSG00000137494 11 82904781 82971736 +
CCDC90B ENSG00000137500 11 82970139 82997450 -
DLG2 ENSG00000150672 11 83166055 85338966 -
Gene symbol Ensembl ID Chromosome Start End Strand
TMEM126B ENSG00000171204 11 85339629 85347580 +
TMEM126A ENSG00000171202 11 85359011 85367591 +
CREBZF ENSG00000137504 11 85370752 85393951 -
CCDC89 ENSG00000179071 11 85394893 85397320 -
SYTL2 ENSG00000137501 11 85405267 85522184 -
AP000974.1 ENSG00000215504 11 85563600 85565986 -
CCDC83 ENSG00000150676 11 85566144 85631064 +
PICALM ENSG00000073921 11 85668727 85780924 -
EED ENSG00000074266 11 85955586 85989781 +
Cllorf73 ENSG00000149196 11 86013253 86056969 +
CCDC81 ENSG00000149201 11 86085778 86134151 +
ME3 ENSG00000151376 11 86152150 86383678 -
PRSS23 ENSG00000150687 11 86502101 86663886 +
FZD4 ENSG00000174804 11 86656721 86666433 -
TMEM135 ENSG00000166575 11 86748886 87034756 +
RAB38 ENSG00000123892 11 87846431 87908635 -
CTSC ENSG00000109861 11 88026778 88070955 -
FAT3 ENSG00000165323 11 92085262 92629618 +
MTNR1B ENSG00000134640 11 92702886 92718232 +
SLC36A4 ENSG00000180773 11 92877341 92931130 -
CCDC67 ENSG00000165325 11 93063137 93171653 +
Cllorf75 ENSG00000166002 11 93211638 93276674 -
KIAA1731 ENSG00000166004 11 93394805 93463522 +
TAF1D ENSG00000166012 11 93463114 93517557 -
Cllorf54 ENSG00000182919 11 93474757 93497915 +
MED17 ENSG00000042429 11 93517393 93547861 +
VSTM5 ENSG00000214376 11 93551398 93583697 -
HEPHL1 ENSG00000181333 11 93754527 93846917 +
PANX1 ENSG00000110218 11 93862094 93915138 +
FOLR4 ENSG00000183560 11 94038759 94040887 +
GPR83 ENSG00000123901 11 94110477 94134585 -
MRE11A ENSG00000020922 11 94152895 94227074 -
ANKRD49 ENSG00000168876 11 94226795 94232749 +
PIWIL4 ENSG00000134627 11 94277006 94354587 +
FUT4 ENSG00000196371 11 94277017 94283063 +
AMOTL1 ENSG00000166025 11 94439597 94609918 +
KDM4D ENSG00000186280 11 94706845 94732682 +
KDM4E ENSG00000235268 11 94758422 94760760 +
ENDOD1 ENSG00000149218 11 94822974 94865809 +
SESN3 ENSG00000149212 11 94898704 94965705 -
FAM76B ENSG00000077458 11 95502106 95523573 -
CEP57 ENSG00000166037 11 95523129 95565857 +
MTMR2 ENSG00000087053 11 95566046 95658479 -
Gene symbol Ensembl ID Chromosome Start End Strand
CNTN5 ENSG00000149972 11 98891683 100229616 +
ARHGAP42 ENSG00000165895 11 100558384 100861656 +
TMEM133 ENSG00000170647 11 100862811 100864663 +
PGR ENSG00000082175 11 100900355 101001255 -
TRPC6 ENSG00000137672 11 101322295 101743293 -
ANGPTL5 ENSG00000187151 11 101761405 101787253 -
KIAA1377 ENSG00000110318 11 101785746 101871789 +
Cllorf70 ENSG00000137691 11 101918174 101955291 +
YAP1 ENSG00000137693 11 101981192 102104154 +
BIRC3 ENSG00000023445 11 102188215 102210134 +
BIRC2 ENSG00000110330 11 102217942 102249401 +
TMEM123 ENSG00000152558 11 102267063 102341115 -
RP11-31506.2 ENSG00000255482 11 102337986 102369532 +
MMP7 ENSG00000137673 11 102391239 102401484 -
MMP20 ENSG00000137674 11 102447566 102496063 -
RP11-817J15.3 ENSG00000255798 11 102552041 102554644 +
MMP27 ENSG00000137675 11 102562218 102576537 -
MMP8 ENSG00000118113 11 102582526 102597781 -
MMP10 ENSG00000166670 11 102641234 102651359 -
MMP1 ENSG00000196611 11 102660651 102668891 -
MMP3 ENSG00000149968 11 102706532 102714534 -
MMP13 ENSG00000137745 11 102813724 102826463 -
DCUN1D5 ENSG00000137692 11 102932805 102962944 -
DYNC2H1 ENSG00000187240 11 102980160 103350591 +
PDGFD ENSG00000170962 11 103777914 104035107 -
DDI1 ENSG00000170967 11 103907308 103909922 +
CASP12 ENSG00000204403 11 104756445 104769397 -
CASP4 ENSG00000196954 11 104813593 104840163 -
CASP5 ENSG00000137757 11 104864962 104893895 -
CASPI ENSG00000137752 11 104896170 104972158 -
CARD16 ENSG00000204397 11 104912053 104972158 -
CARD17 ENSG00000255221 11 104963196 104972158 -
CARD18 ENSG00000255501 11 105008448 105010453 -
GRIA4 ENSG00000152578 11 105480721 105852819 +
MSANTD4 ENSG00000170903 11 105866350 105893130 -
KBTBD3 ENSG00000182359 11 105921825 105948492 -
AASDHPPT ENSG00000149313 11 105946228 105969437 +
GUCY1A2 ENSG00000152402 11 106555148 106889250 -
CWF19L2 ENSG00000152404 11 107197071 107328572 -
ALKBH8 ENSG00000137760 11 107373452 107436472 -
ELMOD1 ENSG00000110675 11 107461817 107537505 +
AP000889.3 ENSG00000268467 11 107462471 107463949 +
SLN ENSG00000170290 11 107578104 107590419 -
Gene symbol Ensembl ID Chromosome Start End Strand
AP002353.1 ENSG00000268602 11 107582998 107595135 +
AP001024.2 ENSG00000214306 11 107643129 107647344 +
AP001024.1 ENSG00000214305 11 107650219 107652316 +
SLC35F2 ENSG00000110660 11 107661717 107799019 -
RAB39A ENSG00000179331 11 107799229 107834208 +
CUL5 ENSG00000166266 11 107879459 107978503 +
ACA 1 ENSG00000075239 11 107992243 108018503 +
NPAT ENSG00000149308 11 108027942 108093369 -
ATM ENSG00000149311 11 108093211 108239829 +
AP001925.1 ENSG00000269042 11 108130255 108136480 -
Cllorf65 ENSG00000166323 11 108179246 108338258 -
KDELC2 ENSG00000178202 11 108342832 108369159 -
EXPH5 ENSG00000110723 11 108376158 108464465 -
DDX10 ENSG00000178105 11 108535752 108811657 +
Cllorf87 ENSG00000185742 11 109292846 109299840 +
ZC3H12C ENSG00000149289 11 109964087 110042566 +
RDX ENSG00000137710 11 110045605 110167447 -
FDX1 ENSG00000137714 11 110300607 110335605 +
ARHGAP20 ENSG00000137727 11 110447766 110583912 -
Cllorf53 ENSG00000150750 11 111126707 111157126 +
Cllorf92 ENSG00000196167 11 111164114 111175770 -
Cllorf93 ENSG00000214290 11 111169565 111179460 +
POU2AF1 ENSG00000110777 11 111222977 111326355 -
RP11-794P6.2 ENSG00000255093 11 111322064 111328876 +
BTG4 ENSG00000137707 11 111338251 111383079 -
Cllorf88 ENSG00000183644 11 111385510 111407756 +
LAYN ENSG00000204381 11 111411005 111432264 +
SIK2 ENSG00000170145 11 111473115 111601577 +
PPP2R1B ENSG00000137713 11 111597632 111637151 -
ALG9 ENSG00000086848 11 111652919 111742305 -
ALG9 ENSG00000258529 11 111657010 111750149 -
FDXACB1 ENSG00000255561 11 111744780 111751967 -
Cllorf1 ENSG00000137720 11 111749659 111756699 +
CRYAB ENSG00000109846 11 111779289 111794446 -
HSPB2 ENSG00000170276 11 111782966 111789574 +
HSPB2- ENSG00000254445 11 111783460 111797595 + Cllorf52
Cllorf52 ENSG00000149300 11 111788756 111797596 +
DIXDCl ENSG00000150764 11 111797868 111893308 +
DLAT ENSG00000150768 11 111895538 111935114 +
PIH1D2 ENSG00000150773 11 111934734 111944998 -
Cllorf57 ENSG00000150776 11 111944810 111955874 +
TIMM8B ENSG00000150779 11 111955524 111957522 -
SDHD ENSG00000204370 11 111957497 111990353 +
Gene symbol Ensembl ID Chromosome Start End Strand
SDHD ENSG00000255292 11 111957627 112071394 +
IL18 ENSG00000150782 11 112013974 112034840 -
TEX12 ENSG00000150783 11 112038095 112043282 +
BC02 ENSG00000197580 11 112046190 112095422 +
PTS ENSG00000150787 11 112097088 112140678 +
SEGMENT-5
WHSC1 ENSG00000109685 4 1873151 1983934 +
WHSC2 ENSG00000185049 4 1984441 2043630 -
C4orf48 ENSG00000243449 4 2043689 2045697 +
NA 8L ENSG00000185818 4 2061239 2070816 +
POLN ENSG00000130997 4 2073645 2243848 -
HAUS3 ENSG00000214367 4 2229191 2243891 -
MXD4 ENSG00000123933 4 2249159 2264021 -
ZFYVE28 ENSG00000159733 4 2271309 2420390 -
RP11-503N18.3 ENSG00000249428 4 2451700 2464668 +
RNF4 ENSG00000063978 4 2463947 2627047 +
FAM193A ENSG00000125386 4 2626988 2734292 +
TNIP2 ENSG00000168884 4 2743375 2758103 -
SH3BP2 ENSG00000087266 4 2794750 2842825 +
ADD1 ENSG00000087274 4 2845584 2931803 +
MFSD10 ENSG00000109736 4 2932288 2936586 -
NOP14 ENSG00000087269 4 2939660 2965112 -
GRK4 ENSG00000125388 4 2965335 3042474 +
HTT ENSG00000197386 4 3076408 3245676 +
MSANTD1 ENSG00000188981 4 3246096 3273465 +
RGS12 ENSG00000159788 4 3294755 3441640 +
HGFAC ENSG00000109758 4 3443614 3451211 +
DOK7 ENSG00000175920 4 3465033 3503200 +
LRPAP1 ENSG00000163956 4 3508103 3534286 -
AL590235.1 ENSG00000268781 4 3511523 3511678 -
RP3-368B9.1 ENSG00000216560 4 3578596 3592712 +
ADRA2C ENSG00000184160 4 3768075 3770251 +
OTOP1 ENSG00000163982 4 4190530 4228616 -
TMEM128 ENSG00000132406 4 4237269 4249950 -
LYAR ENSG00000145220 4 4269428 4291896 -
ZBTB49 ENSG00000168826 4 4291924 4323513 +
NSG1 ENSG00000168824 4 4349867 4420785 +
STX18 ENSG00000168818 4 4417469 4544073 -
MSX1 ENSG00000163132 4 4861393 4865663 +
CYTL1 ENSG00000170891 4 5016313 5021199 -
STK32B ENSG00000152953 4 5053169 5502725 +
C4orf6 ENSG00000082929 4 5526296 5529528 +
EVC2 ENSG00000173040 4 5544499 5711275 -
Gene symbol Ensembl ID Chromosome Start End Strand
EVC ENSG00000072840 4 5712924 5830772 +
CRMP1 ENSG00000072832 4 5749811 5894785 -
C4orf50 ENSG00000181215 4 5958845 5991545 -
JAKMIP1 ENSG00000152969 4 6027926 6202318 -
WFS1 ENSG00000109501 4 6271576 6304992 +
PPP2R2C ENSG00000074211 4 6322305 6565327 -
ΜΆΝ2Β2 ENSG00000013288 4 6576902 6625089 +
MRFAP1 ENSG00000179010 4 6641818 6644472 +
AC093323.1 ENSG00000268791 4 6693782 6694189 -
S100P ENSG00000163993 4 6694796 6698897 +
MRFAP1L1 ENSG00000178988 4 6709428 6711607 -
BLOC1S4 ENSG00000186222 4 6717842 6719387 +
KIAA0232 ENSG00000170871 4 6783102 6885897 +
TBC1D14 ENSG00000132405 4 6910969 7034845 +
CCDC96 ENSG00000173013 4 7042579 7044728 -
TADA2B ENSG00000173011 4 7043626 7058368 +
GRPEL1 ENSG00000109519 4 7060633 7069924 -
SORCS2 ENSG00000184985 4 7194265 7744554 +
PSAPL1 ENSG00000178597 4 7432022 7436700 -
AFAP1 ENSG00000196526 4 7760441 7941653 -
AC097381.1 ENSG00000228919 4 7940728 7942022 +
ABLIM2 ENSG00000163995 4 7967039 8160559 -
SH3TC1 ENSG00000125089 4 8183799 8242830 +
HTRA3 ENSG00000170801 4 8271492 8308838 +
ACOX3 ENSG00000087008 4 8368439 8442450 -
TRM 44 ENSG00000155275 4 8437867 8495258 +
GPR78 ENSG00000155269 4 8560452 8621486 +
CPZ ENSG00000109625 4 8594387 8621488 +
HMX1 ENSG00000215612 4 8847931 8873543 -
WDR1 ENSG00000071127 4 10075963 10118573 -
ZNF518B ENSG00000178163 4 10441498 10459034 -
CLNK ENSG00000109684 4 10488019 10686489 -
HS3ST1 ENSG00000002587 4 11394774 11431389 -
RAB28 ENSG00000157869 4 13362978 13485989 -
NKX3-2 ENSG00000109705 4 13542454 13546674 -
BOD1L1 ENSG00000038219 4 13570362 13629347 -
CPEB2 ENSG00000137449 4 15004298 15071777 +
C1QTNF7 ENSG00000163145 4 15341442 15447790 +
CC2D2A ENSG00000048342 4 15471489 15603180 +
FBXL5 ENSG00000118564 4 15606162 15683302 -
FAM200B ENSG00000237765 4 15683285 15707188 +
BST1 ENSG00000109743 4 15704573 15739936 +
CD38 ENSG00000004468 4 15779898 15851069 +
Gene symbol Ensembl ID Chromosome Start End Strand
FGFBP1 ENSG00000137440 4 15937192 15940363 -
FGFBP2 ENSG00000137441 4 15961866 15970932 -
PROM1 ENSG00000007062 4 15964699 16086001 -
TAP 1 ENSG00000169762 4 16162128 16229033 -
LDB2 ENSG00000169744 4 16503164 16900432 -
QDPR ENSG00000151552 4 17461884 17513857 -
CLRN2 ENSG00000249581 4 17516788 17528727 +
LAP3 ENSG00000002549 4 17578815 17609595 +
MED28 ENSG00000118579 4 17616254 17627477 +
FAM184B ENSG00000047662 4 17630929 17783135 -
DCAF16 ENSG00000163257 4 17802278 17812381 -
NCAPG ENSG00000109805 4 17812525 17846485 +
LCORL ENSG00000178177 4 17844839 18023499 -
SLIT2 ENSG00000145147 4 20254883 20622184 +
PACRGL ENSG00000163138 4 20697905 20754530 +
KCNIP4 ENSG00000185774 4 20730239 21950422 -
GPR125 ENSG00000152990 4 22346694 22517677 -
GBA3 ENSG00000269541 4 22694639 22820546 +
AC093917.1 ENSG00000269222 4 22694639 22820546 +
PPARGC1A ENSG00000109819 4 23756664 23905712 -
DHX15 ENSG00000109606 4 24519064 24586173 -
SOD3 ENSG00000109610 4 24791534 24802464 +
CCDC149 ENSG00000181982 4 24807739 24981826 -
LGI2 ENSG00000153012 4 25000469 25032501 -
SEPSECS ENSG00000109618 4 25121627 25162204 -
PI4K2B ENSG00000038210 4 25162263 25280714 +
ZCCHC4 ENSG00000168228 4 25314407 25372005 +
ANAPC4 ENSG00000053900 4 25378835 25420120 +
SLC34A2 ENSG00000157765 4 25656923 25680370 +
SEL1L3 ENSG00000091490 4 25749055 25865382 -
C4orf52 ENSG00000250317 4 25863452 25931435 +
RBPJ ENSG00000168214 4 26165077 26436541 +
CCKAR ENSG00000163394 4 26483022 26492084 -
TBC1D19 ENSG00000109680 4 26578059 26756973 +
STIM2 ENSG00000109689 4 26859300 27027003 +
RP11-180C1.1 ENSG00000250038 4 28363901 28404486 -
LPHN3 ENSG00000150471 4 62066976 62938184 +
TECRL ENSG00000205678 4 65140975 65275186 -
EPHA5 ENSG00000145242 4 66185281 66536213 -
TMPRSS11F ENSG00000198092 4 68918916 68995598 -
TMPRSS11BNL ENSG00000226894 4 69054242 69083798 -
TMPRSS11B ENSG00000185873 4 69092371 69111438 -
YTHDC1 ENSG00000083896 4 69176105 69215807 -
Gene symbol Ensembl ID Chromosome Start End Strand
TMPRSS11E ENSG00000087128 4 69313167 69363322 +
UGT2B17 ENSG00000197888 4 69402902 69434245 -
UGT2B15 ENSG00000196620 4 69512348 69536346 -
UGT2B10 ENSG00000109181 4 69681711 69696914 +
UGT2A3 ENSG00000135220 4 69794181 69817509 -
UGT2B7 ENSG00000171234 4 69917081 69978705 +
UGT2B11 ENSG00000213759 4 70065669 70080449 -
UGT2B28 ENSG00000135226 4 70146217 70160768 +
UGT2B4 ENSG00000156096 4 70345883 70391732 -
UGT2A1 ENSG00000173610 4 70454135 70518967 -
SULT1B1 ENSG00000173597 4 70592566 70653679 -
SULT1E1 ENSG00000109193 4 70676498 70725870 -
CSN1S1 ENSG00000126545 4 70796799 70812289 +
CSN2 ENSG00000135222 4 70820974 70826725 -
STATH ENSG00000126549 4 70861647 70868287 +
HTN3 ENSG00000205649 4 70894130 70902255 +
HTN1 ENSG00000126550 4 70916119 70924562 +
C4orf40 ENSG00000187533 4 70999333 71042516 +
ODAM ENSG00000109205 4 71062213 71070293 +
FDCSP ENSG00000181617 4 71091788 71100969 +
CSN3 ENSG00000171209 4 71108305 71117145 +
CABSI ENSG00000145309 4 71200698 71202833 +
SMR3A ENSG00000109208 4 71226478 71232875 +
SMR3B ENSG00000171201 4 71235810 71255961 +
PROL1 ENSG00000171199 4 71263599 71275911 +
MUC7 ENSG00000171195 4 71296209 71348714 +
AMTN ENSG00000187689 4 71384257 71398459 +
AMBN ENSG00000178522 4 71457973 71473005 +
ENAM ENSG00000132464 4 71494461 71552533 +
IGJ ENSG00000132465 4 71521258 71547534 -
UTP3 ENSG00000132467 4 71554196 71556267 +
RUFY3 ENSG00000018189 4 71569921 71673032 +
GRSF1 ENSG00000132463 4 71681499 71705662 -
MOBIB ENSG00000173542 4 71768043 71888166 +
DCK ENSG00000156136 4 71858255 71896631 +
SLC4A4 ENSG00000080493 4 72053003 72437804 +
GC ENSG00000145321 4 72607410 72669758 -
NPFFR2 ENSG00000056291 4 72897521 73013784 +
ADAM S3 ENSG00000156140 4 73146686 73434516 -
COX18 ENSG00000163626 4 73921797 73935472 -
ANKRD17 ENSG00000132466 4 73939093 74124515 -
ALB ENSG00000163631 4 74262831 74287129 +
AFP ENSG00000081051 4 74296855 74321891 +
Gene symbol Ensembl ID Chromosome Start End Strand
AFM ENSG00000079557 4 74347400 74369691 +
RASSF6 ENSG00000169435 4 74437267 74486348 -
IL8 ENSG00000169429 4 74606223 74609433 +
CXCL6 ENSG00000124875 4 74702214 74714781 +
PF4V1 ENSG00000109272 4 74718906 74719872 +
CXCL1 ENSG00000163739 4 74735110 74736959 +
PF4 ENSG00000163737 4 74846794 74847841 -
PPBP ENSG00000163736 4 74852755 74853914 -
CXCL5 ENSG00000163735 4 74861359 74864496 -
CXCL3 ENSG00000163734 4 74902306 74904524 -
CXCL2 ENSG00000081041 4 74962793 74965010 -
AC093677.1 ENSG00000269559 4 75023327 75024085 -
BTC ENSG00000174808 4 75669969 75719896 -
PARM1 ENSG00000169116 4 75858305 75975325 +
RCHY1 ENSG00000163743 4 76404247 76439974 -
THAP6 ENSG00000174796 4 76439156 76475683 +
C4orf26 ENSG00000174792 4 76481258 76491095 +
CDKL2 ENSG00000138769 4 76503215 76555900 -
G3BP2 ENSG00000138757 4 76567966 76649709 -
USOl ENSG00000138768 4 76649762 76735382 +
PPEF2 ENSG00000156194 4 76781020 76823724 -
NAAA ENSG00000138744 4 76831809 76862204 -
SDAD1 ENSG00000198301 4 76862103 76912115 -
AC110615.1 ENSG00000268788 4 76871883 76878526 +
CXCL9 ENSG00000138755 4 76922428 76928641 -
ART3 ENSG00000156219 4 76932337 77033955 +
CXCL10 ENSG00000169245 4 76942273 76944650 -
CXCL11 ENSG00000169248 4 76954835 76962568 -
NUP54 ENSG00000138750 4 77035812 77069668 -
SCARB2 ENSG00000138760 4 77079890 77135046 -
FAM47E ENSG00000189157 4 77135193 77232282 +
STBD1 ENSG00000118804 4 77172886 77232752 +
CCDC158 ENSG00000163749 4 77234154 77343021 -
SHROOM3 ENSG00000138771 4 77356253 77704406 +
SOWAHB ENSG00000186212 4 77816082 77819002 -
SEPT11 ENSG00000138758 4 77870856 77961537 +
CCNI ENSG00000118816 4 77968311 77997158 -
CCNG2 ENSG00000138764 4 78078304 78354542 +
CXCL13 ENSG00000156234 4 78432907 78532988 +
CNOT6L ENSG00000138767 4 78634541 78740769 -
MRPL1 ENSG00000169288 4 78783674 78873944 +
FRASl ENSG00000138759 4 78978724 79465423 +
ANXA3 ENSG00000138772 4 79472673 79531597 +
Gene symbol Ensembl ID Chromosome Start End Strand
BMP2K ENSG00000138756 4 79697496 79837526 +
PAQR3 ENSG00000163291 4 79808281 79860592 -
NAA11 ENSG00000156269 4 80146848 80247204 -
GK2 ENSG00000196475 4 80327508 80329372 -
ANTXR2 ENSG00000163297 4 80822303 81046608 -
PRDM8 ENSG00000152784 4 81105033 81125483 +
FGF5 ENSG00000138675 4 81187753 81257834 +
C4orf22 ENSG00000197826 4 81256874 81884910 +
BMP3 ENSG00000152785 4 81952119 81978685 +
PRKG2 ENSG00000138669 4 82009837 82136218 -
RASGEF1B ENSG00000138670 4 82347547 82393082 -
HNRNPD ENSG00000138668 4 83273651 83295656 -
HNRPDL ENSG00000152795 4 83343717 83351294 -
ENOPH1 ENSG00000145293 4 83351715 83382244 +
TMEM150C ENSG00000249242 4 83405743 83483510 -
SCD5 ENSG00000145284 4 83550692 83720010 -
SEC31A ENSG00000138674 4 83739814 83822319 -
THAP9 ENSG00000168152 4 83821837 83841438 +
LIN54 ENSG00000189308 4 83831126 83934079 -
COPS4 ENSG00000138663 4 83955600 83996971 +
PLAC8 ENSG00000145287 4 84011201 84058228 -
COQ2 ENSG00000173085 4 84182689 84206067 -
HPSE ENSG00000173083 4 84213614 84256306 -
HELQ ENSG00000163312 4 84328496 84377009 -
MRPS18C ENSG00000163319 4 84377085 84390888 +
FAM175A ENSG00000163322 4 84382092 84444501 -
AGPA 9 ENSG00000138678 4 84457067 84527028 +
NKX6-1 ENSG00000163623 4 85413061 85419603 -
CDS1 ENSG00000163624 4 85504132 85572491 +
WDFY3 ENSG00000163625 4 85590704 85887544 -
ARHGAP24 ENSG00000138639 4 86396267 86923823 +
MAPK10 ENSG00000109339 4 86936276 87515284 -
PTPN13 ENSG00000163629 4 87515468 87736324 +
SLC10A6 ENSG00000145283 4 87744621 87770416 -
C4orf36 ENSG00000163633 4 87797358 87857354 -
AFF1 ENSG00000172493 4 87856154 88062206 +
KLHL8 ENSG00000145332 4 88081255 88141760 -
HSD17B13 ENSG00000170509 4 88224941 88244058 -
HSD17B11 ENSG00000198189 4 88257762 88312538 -
NUD 9 ENSG00000170502 4 88343734 88380606 +
SPARCLI ENSG00000152583 4 88394487 88452213 -
DSPP ENSG00000152591 4 88529681 88538062 +
DMP1 ENSG00000152592 4 88571459 88585513 +
Gene symbol Ensembl ID Chromosome Start End Strand
IBSP ENSG00000029559 4 88720733 88733074 +
MEPE ENSG00000152595 4 88742563 88767969 +
SPP1 ENSG00000118785 4 88896819 88904562 +
PKD2 ENSG00000118762 4 88928820 88998929 +
ABCG2 ENSG00000118777 4 89011416 89152474 -
PPM1K ENSG00000163644 4 89183315 89205921 -
HERC6 ENSG00000138642 4 89299891 89364263 +
HERC5 ENSG00000138646 4 89378268 89427314 +
PYURF ENSG00000145337 4 89442136 89444964 -
HERC3 ENSG00000138641 4 89442199 89629693 +
PIGY ENSG00000255072 4 89442724 89442940 -
NAP1L5 ENSG00000177432 4 89617066 89619386 -
FAM13A ENSG00000138640 4 89647106 90032549 -
TIGD2 ENSG00000180346 4 90033968 90036050 +
GPRIN3 ENSG00000185477 4 90165429 90229161 -
SNCA ENSG00000145335 4 90645250 90759466 -
MMRN1 ENSG00000138722 4 90800683 90875780 +
FAM190A ENSG00000184305 4 91048686 92523064 +
RP11-763F8.1 ENSG00000249049 4 92240185 92246457 -
RP11-9B6.1 ENSG00000248511 4 93218402 93225329 -
GRID2 ENSG00000152208 4 93225550 94695707 +
ATOH1 ENSG00000172238 4 94750042 94751221 +
SMARCAD1 ENSG00000163104 4 95128762 95212443 +
HPGDS ENSG00000163106 4 95219686 95264027 -
PDLIM5 ENSG00000163110 4 95373037 95589377 +
BMPR1B ENSG00000138696 4 95679119 96079599 +
UNC5C ENSG00000182168 4 96083655 96470357 -
PDHA2 ENSG00000163114 4 96761239 96762625 +
TENM3 ENSG00000218336 4 183065140 183724177 +
DCTD ENSG00000129187 4 183811213 183839089 -
WWC2 ENSG00000151718 4 184020446 184241930 +
CLDN22 ENSG00000177300 4 184239220 184241927 -
CLDN24 ENSG00000185758 4 184242917 184243579 -
CDKN2AIP ENSG00000168564 4 184365744 184369351 +
ING2 ENSG00000168556 4 184426147 184432249 +
RWDD4 ENSG00000182552 4 184560788 184580378 -
TRAPPCll ENSG00000168538 4 184580420 184634745 +
STOX2 ENSG00000173320 4 184774584 184944679 +
ENPP6 ENSG00000164303 4 185009859 185142383 -
IRF2 ENSG00000168310 4 185308867 185395734 -
CASP3 ENSG00000164305 4 185548850 185570663 -
CCDC111 ENSG00000164306 4 185570767 185616117 +
MLF1IP ENSG00000151725 4 185615772 185655287 -
Gene symbol Ensembl ID Chromosome Start End Strand
ACSL1 ENSG00000151726 4 185676749 185747972 -
RP11-701P16.2 ENSG00000251139 4 185734773 185742443 +
HELT ENSG00000187821 4 185939995 185941958 +
SLC25A4 ENSG00000151729 4 186064395 186068434 +
KIAA1430 ENSG00000164323 4 186080819 186130658 -
SNX25 ENSG00000109762 4 186125391 186291339 +
LRP2BP ENSG00000109771 4 186285032 186317053 -
ANKRD37 ENSG00000186352 4 186317175 186321782 +
UFSP2 ENSG00000109775 4 186320694 186347139 -
C4orf47 ENSG00000205129 4 186347394 186370980 +
CCDC110 ENSG00000168491 4 186366336 186392913 -
RP11-27909.4 ENSG00000249679 4 186392670 186393417 +
PDLIM3 ENSG00000154553 4 186422903 186456766 -
SORBS2 ENSG00000154556 4 186506598 186877806 -
TLR3 ENSG00000164342 4 186990306 187006255 +
FAM149A ENSG00000109794 4 187025573 187093821 +
AC110771.1 ENSG00000269302 4 187111913 187112626 -
CYP4V2 ENSG00000145476 4 187112674 187134610 +
KLKB1 ENSG00000164344 4 187130133 187179625 +
Fll ENSG00000088926 4 187187099 187210835 +
MTNR1A ENSG00000168412 4 187347700 187476721 -
FA 1 ENSG00000083857 4 187508937 187647876 -
SEGMENT-6
TBC1D4 ENSG00000136111 13 75858808 76056250 -
COMMD6 ENSG00000188243 13 76099350 76123575 -
UCHL3 ENSG00000118939 13 76123619 76180085 +
LM07 ENSG00000136153 13 76194570 76434004 +
C13orf45 ENSG00000178734 13 76445187 76457947 +
KCTD12 ENSG00000178695 13 77454312 77460540 -
IRG1 ENSG00000102794 13 77522632 77532777 +
CLN5 ENSG00000102805 13 77564795 77576652 +
FBXL3 ENSG00000005812 13 77566740 77601330 -
MYCBP2 ENSG00000005810 13 77618792 77901185 -
SCEL ENSG00000136155 13 78109809 78219398 +
SLAIN1 ENSG00000139737 13 78272023 78338377 +
SEGMENT-7
EDNRB ENSG00000136160 13 78469616 78493903 -
POU4F1 ENSG00000152192 13 79173227 79177673 -
RNF219 ENSG00000152193 13 79188426 79233314 -
RBM26 ENSG00000139746 13 79885962 79980612 -
NDFIP2 ENSG00000102471 13 80055287 80130210 +
SPRY2 ENSG00000136158 13 80910111 80915086 -
SLITRK6 ENSG00000184564 13 86366925 86373623 -
Gene symbol Ensembl ID Chromosome Start End Strand
SLITRK5 ENSG00000165300 13 88324870 88331868 +
GPC5 ENSG00000179399 13 92050929 93519490 +
0XGR1 ENSG00000165621 13 97637973 97646984 -
MBNL2 ENSG00000139793 13 97873688 98046374 +
RAP2A ENSG00000125249 13 98086476 98120244 +
IP05 ENSG00000065150 13 98605742 98676551 +
FARPI ENSG00000152767 13 98794816 99102027 +
RNF113B ENSG00000139797 13 98828039 98829519 -
STK24 ENSG00000102572 13 99102455 99230194 -
SLC15A1 ENSG00000088386 13 99336898 99404908 -
DOCK9 ENSG00000088387 13 99445741 99738879 -
UBAC2 ENSG00000134882 13 99853028 100038688 +
GPR18 ENSG00000125245 13 99906968 99913998 -
GPR183 ENSG00000169508 13 99946784 99959659 -
TM9SF2 ENSG00000125304 13 100153671 100215645 +
CLYBL ENSG00000125246 13 100258919 100549387 +
ZIC5 ENSG00000139800 13 100617451 100624163 -
ZIC2 ENSG00000043355 13 100634026 100639018 +
NALCN ENSG00000102452 13 101706130 102068843 -
ITGBL1 ENSG00000198542 13 102104966 102371145 +
FGF14 ENSG00000102466 13 102375035 103054124 -
TPP2 ENSG00000134900 13 103249353 103331521 +
METTL21C ENSG00000139780 13 103338097 103346854 -
CCDC168 ENSG00000175820 13 103381801 103389159 -
TEX30 ENSG00000151287 13 103418340 103426161 -
KDELC1 ENSG00000134901 13 103436631 103451357 -
BIVM ENSG00000134897 13 103451399 103493885 +
ERCC5 ENSG00000134899 13 103497194 103528345 +
SLC10A2 ENSG00000125255 13 103696350 103719196 -
DAOA ENSG00000182346 13 106118216 106143383 +
EFNB2 ENSG00000125266 13 107142093 107187462 -
ARGLU1 ENSG00000134884 13 107194021 107220512 -
MY016 ENSG00000041515 13 109248500 109860355 +
IRS2 ENSG00000185950 13 110406184 110438915 -
COL4A1 ENSG00000187498 13 110801318 110959496 -
COL4A2 ENSG00000134871 13 110958159 111165374 +
COL4A2-AS2 ENSG00000224821 13 111108743 111120763 -
RAB20 ENSG00000139832 13 111175417 111214080 -
CARKD ENSG00000213995 13 111267881 111292340 +
CARS2 ENSG00000134905 13 111293759 111365950 -
ING1 ENSG00000153487 13 111365083 111373421 +
LINC00346 ENSG00000255874 13 111521578 111522162 -
ANKRD10 ENSG00000088448 13 111530887 111567416 -
Gene symbol Ensembl ID Chromosome Start End Strand
SEGMENT-8
FTSJD1 ENSG00000180917 16 71315292 71323618 -
CALB2 ENSG00000172137 16 71392616 71424341 +
ZNF23 ENSG00000167377 16 71481500 71496998 -
ZNF19 ENSG00000261611 16 71481503 71523214 -
ZNF19 ENSG00000157429 16 71498453 71598992 -
CHST4 ENSG00000140835 16 71559136 71572649 +
TAT ENSG00000198650 16 71599563 71611033 -
MARVELD3 ENSG00000140832 16 71660064 71676017 +
PHLPP2 ENSG00000040199 16 71671738 71758604 -
AP1G1 ENSG00000166747 16 71762913 71843104 -
ATXN1L ENSG00000224470 16 71879894 71891231 +
IST1 ENSG00000261750 16 71879899 71950997 +
ZNF821 ENSG00000102984 16 71893583 71929239 -
IST1 ENSG00000182149 16 71919136 71962913 +
DHODH ENSG00000102967 16 72042487 72058954 +
TXNL4B ENSG00000140830 16 72078188 72128330 -
HP ENSG00000257017 16 72088491 72094954 +
HPR ENSG00000261701 16 72088522 72111145 +
DHX38 ENSG00000140829 16 72127461 72146811 +
PMFBP1 ENSG00000118557 16 72146056 72210777 -
SEGMENT-9
NRG3 ENSG00000185737 10 83635070 84746723 +
GHITM ENSG00000165678 10 85899196 85913001 +
ClOorf99 ENSG00000188373 10 85933494 85945050 +
CDHR1 ENSG00000148600 10 85954410 85979377 +
LRIT2 ENSG00000204033 10 85980327 85985345 -
LRIT1 ENSG00000148602 10 85991349 86001217 -
RGR ENSG00000148604 10 86004809 86019716 +
FAM190B ENSG00000107771 10 86088342 86278273 +
GRID1 ENSG00000182771 10 87359312 88126250 -
WAPAL ENSG00000062650 10 88195013 88281572 -
OPN4 ENSG00000122375 10 88414314 88426605 +
MINPP1 ENSG00000107789 10 89264632 89313217 +
PAPSS2 ENSG00000198682 10 89419370 89507462 +
ATAD1 ENSG00000138138 10 89511269 89601100 -
KLLN ENSG00000227268 10 89618918 89623194 -
PTEN ENSG00000171862 10 89622870 89731687 +
RNLS ENSG00000184719 10 90033621 90344287 -
LIPJ ENSG00000204022 10 90346510 90366733 +
LIPF ENSG00000182333 10 90424198 90438571 +
LIPK ENSG00000204021 10 90484301 90512543 +
LIPN ENSG00000204020 10 90519952 90537999 +
Gene symbol Ensembl ID Chromosome Start End Strand
LIPM ENSG00000173239 10 90562654 90580303 +
ANKRD22 ENSG00000152766 10 90581889 90611575 -
STAMBPL1 ENSG00000138134 10 90639491 90734910 +
ACTA2 ENSG00000107796 10 90694831 90751147 -
FAS ENSG00000026103 10 90750414 90775542 +
CH25H ENSG00000138135 10 90965694 90967071 -
LI PA ENSG00000107798 10 90973326 91174382 -
IFIT2 ENSG00000119922 10 91061712 91069033 +
IFIT3 ENSG00000119917 10 91087651 91100728 +
IFIT1B ENSG00000204010 10 91137813 91144962 +
IFIT1 ENSG00000185745 10 91152303 91163745 +
IFIT5 ENSG00000152778 10 91174343 91180758 +
SLC16A12 ENSG00000152779 10 91190051 91316398 -
PANK1 ENSG00000152782 10 91342745 91405215 -
KIF20B ENSG00000138182 10 91461367 91534700 +
HTR7 ENSG00000148680 10 92500580 92617455 -
RPP30 ENSG00000148688 10 92631473 92668312 +
ANKRD1 ENSG00000148677 10 92671853 92681033 -
PCGF5 ENSG00000180628 10 92979908 93044088 +
HECTD2 ENSG00000165338 10 93170096 93274586 +
PPP1R3C ENSG00000119938 10 93388199 93392811 -
TNKS2 ENSG00000107854 10 93558069 93625033 +
FGFBP3 ENSG00000174721 10 93666346 93669240 -
BTAF1 ENSG00000095564 10 93683526 93790082 +
CPEB3 ENSG00000107864 10 93808399 94050844 -
MARCH5 ENSG00000198060 10 94050920 94113721 +
IDE ENSG00000119912 10 94211441 94333833 -
KIF11 ENSG00000138160 10 94353043 94415150 +
HHEX ENSG00000152804 10 94447945 94455403 +
EXOC6 ENSG00000138190 10 94590935 94819250 +
CYP26C1 ENSG00000187553 10 94821021 94828454 +
CYP26A1 ENSG00000095596 10 94833232 94837647 +
MYOF ENSG00000138119 10 95066186 95242074 -
CEP55 ENSG00000138180 10 95256389 95288849 +
03FAR1 ENSG00000186188 10 95326422 95349829 +
RBP4 ENSG00000138207 10 95351444 95361501 -
PDE6C ENSG00000095464 10 95372345 95425767 +
FRAIOACI ENSG00000148690 10 95427640 95462329 -
LGI1 ENSG00000108231 10 95517566 95557916 +
SLC35G1 ENSG00000176273 10 95653730 95715819 +
PLCE1 ENSG00000138193 10 95753746 96088149 +
NOC3L ENSG00000173145 10 96075004 96122716 -
TBC1D12 ENSG00000108239 10 96162261 96295687 +
Gene symbol Ensembl ID Chromosome Start End Strand
HELLS ENSG00000119969 10 96305547 96373662 +
CYP2C18 ENSG00000108242 10 96442710 96495947 +
CYP2C19 ENSG00000165841 10 96447911 96613017 +
CYP2C9 ENSG00000138109 10 96698415 96749147 +
CYP2C8 ENSG00000138115 10 96796530 96829254 -
C10orfl29 ENSG00000173124 10 96953957 96988685 +
PDLIM1 ENSG00000107438 10 96997329 97050781 -
SORBS1 ENSG00000095637 10 97071528 97321171 -
RP11-476E15.3 ENSG00000212950 10 97114703 97117003 -
ALDH18A1 ENSG00000059573 10 97365696 97416463 -
TCTN3 ENSG00000119977 10 97423153 97454712 -
ENTPD1 ENSG00000138185 10 97454774 97637023 +
ClOorf131 ENSG00000173088 10 97620305 97793507 +
CC2D2B ENSG00000188649 10 97709744 97792441 +
CCNJ ENSG00000107443 10 97803151 97820627 +
BLNK ENSG00000095585 10 97951458 98031333 -
DNTT ENSG00000107447 10 98064085 98098321 +
OPALIN ENSG00000197430 10 98102973 98119092 -
TLL2 ENSG00000095587 10 98124363 98273675 -
TM9SF3 ENSG00000077147 10 98277866 98347209 -
PIK3AP1 ENSG00000155629 10 98353069 98480271 -
LCOR ENSG00000196233 10 98592017 98740800 +
C10orfl2 ENSG00000155640 10 98741041 98745582 +
SLIT1 ENSG00000187122 10 98757795 98945677 -
ARHGAP19 ENSG00000213390 10 98757795 99052413 -
FRA l ENSG00000165879 10 99079022 99081672 +
FRA 2 ENSG00000181274 10 99092255 99094458 -
RRP12 ENSG00000052749 10 99116115 99161127 -
AL355490.1 ENSG00000224474 10 99179228 99185831 -
PGAM1 ENSG00000171314 10 99185917 99193198 +
EXOSC1 ENSG00000171311 10 99190928 99205774 -
ZDHHC16 ENSG00000171307 10 99205927 99217127 +
MMS19 ENSG00000155229 10 99218081 99258551 -
UBTD1 ENSG00000165886 10 99258625 99330966 +
ANKRD2 ENSG00000165887 10 99332198 99343641 +
HOGA1 ENSG00000241935 10 99344080 99372559 +
PI4K2A ENSG00000249967 10 99344131 99433667 +
PI4K2A ENSG00000155252 10 99344131 99436191 +
C10orf62 ENSG00000203942 10 99349450 99350690 +
MORN4 ENSG00000171160 10 99374310 99393852 -
AVPI1 ENSG00000119986 10 99437181 99447080 -
MARVELD1 ENSG00000155254 10 99472930 99484694 +
ZFYVE27 ENSG00000155256 10 99496878 99520663 +
Gene symbol Ensembl ID Chromosome Start End Strand
SFRP5 ENSG00000120057 10 99526508 99531709 -
G0LGA7B ENSG00000155265 10 99609996 99627782 +
CR AC1 ENSG00000095713 10 99624757 99790585 -
AL358938.1 ENSG00000269783 10 99627889 99631294 +
R3HCC1L ENSG00000166024 10 99894387 100004654 +
LOXL4 ENSG00000138131 10 100007447 100028007 -
PYROXD2 ENSG00000119943 10 100143322 100174941 -
HPS1 ENSG00000107521 10 100175955 100206684 -
HPSE2 ENSG00000172987 10 100218875 100995619 -
CNNM1 ENSG00000119946 10 101088856 101154087 +
GO 1 ENSG00000120053 10 101156627 101190381 -
NKX2-3 ENSG00000119919 10 101292690 101296278 +
SLC25A28 ENSG00000155287 10 101370282 101380535 -
ENTPD7 ENSG00000198018 10 101419263 101465997 +
CUTC ENSG00000119929 10 101462315 101515891 +
COX15 ENSG00000014919 10 101471601 101491866 -
ABCC2 ENSG00000023839 10 101542489 101611949 +
DNMBP ENSG00000107554 10 101635334 101769676 -
CPN1 ENSG00000120054 10 101801950 101841634 -
ERLIN1 ENSG00000107566 10 101909851 101948091 -
CHUK ENSG00000213341 10 101948055 101989376 -
CWF19L1 ENSG00000095485 10 101992050 102027437 -
BLOC1S2 ENSG00000196072 10 102033713 102046469 -
PKD2L1 ENSG00000107593 10 102047903 102090243 -
SCD ENSG00000099194 10 102106877 102124591 +
WN 8B ENSG00000075290 10 102222798 102243501 +
SEC31B ENSG00000075826 10 102246399 102289628 -
NDUFB8 ENSG00000255339 10 102265385 102289638 -
NDUFB8 ENSG00000166136 10 102267203 102289757 -
HIF1AN ENSG00000166135 10 102288829 102309763 +
PAX2 ENSG00000075891 10 102495360 102589698 +
FAM178A ENSG00000119906 10 102672720 102724893 +
MRPL43 ENSG00000055950 10 102729215 102747272 -
SEMA4G ENSG00000095539 10 102729275 102745628 +
C10orf2 ENSG00000107815 10 102747124 102754158 +
LZTS2 ENSG00000107816 10 102756375 102767593 +
PDZD7 ENSG00000186862 10 102767567 102790890 -
SFXN3 ENSG00000107819 10 102790991 102800998 +
KAZALD1 ENSG00000107821 10 102821598 102827888 +
HUG1 ENSG00000269259 10 102882536 102883624 +
TLX1 ENSG00000107807 10 102889257 102897545 +
LBX1 ENSG00000138136 10 102986733 102989551 -
BTRC ENSG00000166167 10 103113820 103317078 +
Gene symbol Ensembl ID Chromosome Start End Strand
DPCD ENSG00000166171 10 103330317 103369425 +
POLL ENSG00000166169 10 103338639 103348027 -
FBXW4 ENSG00000107829 10 103370423 103455110 -
FGF8 ENSG00000107831 10 103530081 103535827 -
NPM3 ENSG00000107833 10 103541082 103543170 -
MGEA5 ENSG00000198408 10 103544200 103578696 -
KCNIP2 ENSG00000120049 10 103585731 103603677 -
C10orf76 ENSG00000120029 10 103605356 103815950 -
HPS6 ENSG00000166189 10 103825147 103827792 +
LDB1 ENSG00000198728 10 103867317 103880210 -
PPRC1 ENSG00000148840 10 103892787 103910082 +
NOLC1 ENSG00000166197 10 103911933 103923627 +
ELOVL3 ENSG00000119915 10 103986085 103989346 +
PITX3 ENSG00000107859 10 103989943 104001231 -
GBF1 ENSG00000107862 10 104005289 104142656 +
NFKB2 ENSG00000077150 10 104153867 104162281 +
PSD ENSG00000059915 10 104162376 104181296 -
FBXL15 ENSG00000107872 10 104178946 104182893 +
CUEDC2 ENSG00000107874 10 104183002 104192418 -
ClOorf95 ENSG00000120055 10 104209594 104211300 -
TMEM180 ENSG00000138111 10 104221149 104236802 +
ACTR1A ENSG00000138107 10 104238986 104262482 -
SUFU ENSG00000107882 10 104263744 104393292 +
TRIM8 ENSG00000171206 10 104404252 104418164 +
ARL3 ENSG00000138175 10 104436315 104474164 -
SFXN2 ENSG00000156398 10 104474297 104498951 +
WBP1L ENSG00000166272 10 104503727 104576021 +
CYP17A1 ENSG00000148795 10 104590288 104597290 -
C10orf32 ENSG00000166275 10 104613980 104632990 +
AS3MT ENSG00000214435 10 104629273 104661656 +
CNNM2 ENSG00000148842 10 104678071 104838344 +
NT5C2 ENSG00000076685 10 104845940 104953056 -
INA ENSG00000148798 10 105036920 105050108 +
PCGF6 ENSG00000156374 10 105062553 105110891 -
TAF5 ENSG00000148835 10 105127724 105148822 +
USMG5 ENSG00000173915 10 105148798 105156223 -
PDCD11 ENSG00000148843 10 105156405 105206049 +
CALHM2 ENSG00000138172 10 105206543 105212660 -
CALHM1 ENSG00000185933 10 105213144 105218645 -
CALHM3 ENSG00000183128 10 105232561 105238997 -
NEURL ENSG00000107954 10 105253736 105352309 +
SH3PXD2A ENSG00000107957 10 105348285 105615301 -
OBFC1 ENSG00000107960 10 105642300 105677963 -
Gene symbol Ensembl ID Chromosome Start End Strand
SLK ENSG00000065613 10 105726959 105788991 +
COL17A1 ENSG00000065618 10 105791044 105845760 -
SFR1 ENSG00000156384 10 105881816 105886143 +
WDR96 ENSG00000197748 10 105889646 105992120 -
GSTOl ENSG00000148834 10 105995114 106027217 +
GST02 ENSG00000065621 10 106028631 106059616 +
ITPRIP ENSG00000148841 10 106071894 106098162 -
CCDC147 ENSG00000120051 10 106113522 106214848 +
SORCS3 ENSG00000156395 10 106400859 107024993 +
SORCS1 ENSG00000108018 10 108336940 108924292 -
XPNPEP1 ENSG00000108039 10 111624524 111683311 -
RP11-451M19.3 ENSG00000203876 10 111701029 111713649 -
ADD3 ENSG00000148700 10 111756126 111895323 +
MXI1 ENSG00000119950 10 111967363 112047123 +
SMNDC1 ENSG00000119953 10 112052798 112064709 -
DUSP5 ENSG00000138166 10 112257596 112271302 +
SMC3 ENSG00000108055 10 112327449 112364394 +
RBM20 ENSG00000203867 10 112404155 112599227 +
PDCD4 ENSG00000150593 10 112631565 112659764 +
BBIP1 ENSG00000214413 10 112658488 112679032 -
SHOC2 ENSG00000108061 10 112679301 112773425 +
ADRA2A ENSG00000150594 10 112836790 112840658 +
GPAM ENSG00000119927 10 113909624 113975135 -
TECTB ENSG00000119913 10 114043493 114064793 +
ACSL5 ENSG00000197142 10 114133776 114188138 +
ZDHHC6 ENSG00000023041 10 114190058 114206672 -
VTI1A ENSG00000151532 10 114206756 114578503 +
TCF7L2 ENSG00000148737 10 114710009 114927437 +
HABP2 ENSG00000148702 10 115310596 115349361 +
NRAP ENSG00000197893 10 115348475 115423805 -
CASP7 ENSG00000165806 10 115438942 115490662 +
PLEKHS1 ENSG00000148735 10 115511213 115543188 +
DCLRE1A ENSG00000198924 10 115594488 115614142 -
NHLRC2 ENSG00000196865 10 115614420 115676953 +
AL162407.1 ENSG00000234631 10 115674530 115676949 +
ADRB1 ENSG00000043591 10 115803806 115806667 +
ClOorf118 ENSG00000165813 10 115880621 115933979 -
TDRD1 ENSG00000095627 10 115939029 115992063 +
VWA2 ENSG00000165816 10 115999089 116051272 +
AFAP1L2 ENSG00000169129 10 116054583 116164515 -
ABLIM1 ENSG00000099204 10 116190872 116444414 -
FAM160B1 ENSG00000151553 10 116581503 116659591 +
TRUB1 ENSG00000165832 10 116697952 116737430 +
Gene symbol Ensembl ID Chromosome Start End Strand
ATRNL1 ENSG00000107518 10 116853124 117708503 +
GFRA1 ENSG00000151892 10 117816444 118033126 -
CCDC172 ENSG00000182645 10 118083940 118139541 +
PNLIPRP3 ENSG00000203837 10 118187379 118237469 +
PNLIP ENSG00000175535 10 118305443 118327367 +
PNLIPRP1 ENSG00000187021 10 118349897 118368687 +
C10orf82 ENSG00000165863 10 118423207 118429775 -
HSPA12A ENSG00000165868 10 118430703 118502085 -
EN04 ENSG00000188316 10 118609023 118671297 +
KIAA1598 ENSG00000187164 10 118643742 118886097 -
VAX1 ENSG00000148704 10 118888032 118897812 -
KCNK18 ENSG00000186795 10 118957000 118969810 +
SLC18A2 ENSG00000165646 10 119000604 119038941 +
PDZD8 ENSG00000165650 10 119040000 119134978 -
EMX2 ENSG00000170370 10 119301955 119309441 +
RAB11FIP2 ENSG00000107560 10 119764427 119806114 -
FAM204A ENSG00000165669 10 120065401 120101840 -
PRLHR ENSG00000119973 10 120352916 120355160 -
CACUL1 ENSG00000151893 10 120433679 120514761 -
NANOS1 ENSG00000188613 10 120789228 120793854 +
EIF3A ENSG00000107581 10 120794356 120840396 -
FAM45A ENSG00000119979 10 120863598 120897496 +
SFXN4 ENSG00000183605 10 120900279 120925179 -
PRDX3 ENSG00000165672 10 120927215 120938345 -
GRK5 ENSG00000198873 10 120967101 121215131 +
RGS10 ENSG00000148908 10 121259340 121302220 -
TIAL1 ENSG00000151923 10 121334199 121356541 -
BAG3 ENSG00000151929 10 121410882 121437331 +
INPP5F ENSG00000198825 10 121485609 121588652 +
MCMBP ENSG00000197771 10 121588972 121652068 -
SEC23IP ENSG00000107651 10 121652223 121702014 +
PPAPDC1A ENSG00000203805 10 122216466 122349367 +
C10orf85 ENSG00000177234 10 122357721 122359629 +
WDR11 ENSG00000120008 10 122610695 122669036 +
FGFR2 ENSG00000066468 10 123237848 123357972 -
ATE1 ENSG00000107669 10 123499939 123688316 -
NSMCE4A ENSG00000107672 10 123716603 123734732 -
TACC2 ENSG00000138162 10 123748689 124014060 +
BTBD16 ENSG00000138152 10 124030821 124097677 +
PLEKHA1 ENSG00000107679 10 124134173 124191867 +
ARMS2 ENSG00000254636 10 124214169 124216868 +
HTRAl ENSG00000166033 10 124221041 124274424 +
DMB 1 ENSG00000187908 10 124320181 124403252 +
Gene symbol Ensembl ID Chromosome Start End Strand
C10orfl20 ENSG00000183559 10 124457225 124459338 -
CUZD1 ENSG00000138161 10 124591665 124639146 -
FAM24B ENSG00000213185 10 124608594 124639157 -
FAM24A ENSG00000203795 10 124670217 124672627 +
C10orf88 ENSG00000119965 10 124690419 124713919 -
PSTK ENSG00000179988 10 124713897 124757029 +
IKZF5 ENSG00000095574 10 124750322 124768333 -
ACADSB ENSG00000196177 10 124768495 124817827 +
HMX3 ENSG00000188620 10 124895478 124899995 +
HMX2 ENSG00000188816 10 124907638 124910188 +
BUB3 ENSG00000154473 10 124913793 124924886 +
GPR26 ENSG00000154478 10 125425871 125454123 +
CPXM2 ENSG00000121898 10 125465729 125699783 -
CHST15 ENSG00000182022 10 125767184 125853206 -
OAT ENSG00000065154 10 126085872 126107545 -
NKX1-2 ENSG00000229544 10 126135592 126138753 -
LHPP ENSG00000107902 10 126150403 126306457 +
RP11-12J10.3 ENSG00000258539 10 126305649 126480296 -
FAM53B ENSG00000189319 10 126307861 126432838 -
METTL10 ENSG00000203791 10 126436721 126480446 -
FAM175B ENSG00000165660 10 126490354 126525239 +
ZRANB1 ENSG00000019995 10 126630692 126676758 +
CTBP2 ENSG00000175029 10 126676421 126849739 -
TEX36 ENSG00000175018 10 127265091 127371713 -
C10orfl37 ENSG00000107938 10 127408084 127452712 +
AL158835.1 ENSG00000214294 10 127445352 127445665 +
MMP21 ENSG00000154485 10 127455022 127464390 -
UROS ENSG00000188690 10 127477146 127511817 -
BCCIP ENSG00000107949 10 127512115 127542264 +
DHX32 ENSG00000089876 10 127524906 127585005 -
FANK1 ENSG00000203780 10 127585108 127698161 +
NPS ENSG00000214285 10 129347613 129350935 +
FOX12 ENSG00000186766 10 129535499 129539450 +
PTPRE ENSG00000132334 10 129705325 129884119 +
MKI67 ENSG00000148773 10 129894923 129924649 -
MGMT ENSG00000170430 10 131265448 131566271 +
AL355531.2 ENSG00000268421 10 131308884 131309525 -
EBF3 ENSG00000108001 10 131633547 131762538 -
GLRX3 ENSG00000108010 10 131934663 131982785 +
SEGMENT-10
BBC3 ENSG00000105327 19 47724081 47736023 -
CCDC9 ENSG00000105321 19 47759237 47775210 +
PRR24 ENSG00000257704 19 47778142 47778979 +
Gene symbol Ensembl ID Chromosome Start End Strand
C5AR1 ENSG00000197405 19 47793280 47825323 +
GPR77 ENSG00000134830 19 47835404 47846606 +
DHX34 ENSG00000134815 19 47852538 47889887 +
MEI S3 ENSG00000105419 19 47906316 47922780 -
SLC8A2 ENSG00000118160 19 47931274 47975425 -
KPTN ENSG00000118162 19 47978401 47987525 -
NAPA ENSG00000105402 19 47990894 48018497 -
ZNF541 ENSG00000118156 19 48023942 48059113 -
GLTSCR1 ENSG00000063169 19 48111453 48206533 +
EHD2 ENSG00000024422 19 48216600 48246391 +
GLTSCR2 ENSG00000105373 19 48248779 48260315 +
SEPW1 ENSG00000178980 19 48281829 48287943 +
TPRX1 ENSG00000178928 19 48304500 48322308 -
CCDC114 ENSG00000105479 19 48799714 48825130 -
EMP3 ENSG00000142227 19 48824766 48833810 +
TMEM143 ENSG00000161558 19 48835613 48867494 -
SYNGR4 ENSG00000105467 19 48867652 48879633 +
KDELR1 ENSG00000105438 19 48885827 48894810 -
GRIN2D ENSG00000105464 19 48898132 48948188 +
GRWD1 ENSG00000105447 19 48949030 48960279 +
KCNJ14 ENSG00000182324 19 48958766 48969367 +
CTC-273B12.7 ENSG00000268465 19 48969094 48975688 +
CYTH2 ENSG00000105443 19 48972289 48985571 +
LMTK3 ENSG00000142235 19 48988528 49016446 -
SULT2B1 ENSG00000088002 19 49055332 49102682 +
FAM83E ENSG00000105523 19 49104067 49118111 -
SPACA4 ENSG00000177202 19 49110000 49110970 +
RPL18 ENSG00000063177 19 49118585 49122793 -
SPHK2 ENSG00000063176 19 49122548 49133974 +
DBP ENSG00000105516 19 49133287 49140695 -
CA11 ENSG00000063180 19 49141199 49149569 -
NTN5 ENSG00000142233 19 49164664 49176338 -
FUT2 ENSG00000176920 19 49199228 49209207 +
MAMSTR ENSG00000176909 19 49215999 49222978 -
RASIPl ENSG00000105538 19 49223844 49243978 -
IZUMOl ENSG00000182264 19 49244109 49250166 -
FU 1 ENSG00000174951 19 49251268 49258647 -
FGF21 ENSG00000105550 19 49258816 49261587 +
BCA 2 ENSG00000105552 19 49298322 49314320 -
HSD17B14 ENSG00000087076 19 49316274 49339935 -
PLEKHA4 ENSG00000105559 19 49340354 49371889 -
PPP1R15A ENSG00000087074 19 49375649 49379314 +
TULP2 ENSG00000104804 19 49384222 49401990 -
Gene symbol Ensembl ID Chromosome Start End Strand
NUCB1 ENSG00000104805 19 49403307 49426629 +
DHDH ENSG00000104808 19 49436939 49448226 +
BAX ENSG00000087088 19 49458072 49465055 +
FTL ENSG00000087086 19 49468558 49470135 +
GYS1 ENSG00000104812 19 49471382 49496567 -
RUVBL2 ENSG00000183207 19 49496705 49519252 +
LHB ENSG00000104826 19 49519237 49520338 -
CGB ENSG00000104827 19 49526127 49527590 -
CTB-60B18.6 ENSG00000267335 19 49526210 49540152 -
CGB2 ENSG00000104818 19 49535169 49536495 +
CGB1 ENSG00000267631 19 49538826 49552006 -
CGB5 ENSG00000189052 19 49547141 49548568 +
CGB8 ENSG00000213030 19 49550895 49552400 -
CGB7 ENSG00000196337 19 49557531 49562117 -
NTF4 ENSG00000225950 19 49559050 49568333 -
KCNA7 ENSG00000104848 19 49570675 49576198 -
SNRNP70 ENSG00000104852 19 49588676 49611862 +
LIN7B ENSG00000104863 19 49617581 49621717 +
C19orf73 ENSG00000221916 19 49621655 49622397 -
PPFIA3 ENSG00000177380 19 49622663 49654278 +
HRC ENSG00000130528 19 49654455 49658681 -
TRPM4 ENSG00000130529 19 49660998 49715093 +
SLC6A16 ENSG00000063127 19 49792895 49828482 -
AC011450.1 ENSG00000197813 19 49831424 49843559 -
CD37 ENSG00000104894 19 49838428 49846592 +
TEAD2 ENSG00000074219 19 49843852 49865714 -
DKKL1 ENSG00000104901 19 49865040 49878373 +
CCDC155 ENSG00000161609 19 49891475 49921251 +
PTH2 ENSG00000142538 19 49925671 49926698 -
CTD-3148I10.1 ENSG00000261949 19 49927006 49932075 +
SLC17A7 ENSG00000104888 19 49932658 49945617 -
PIH1D1 ENSG00000104872 19 49949555 49956754 -
ALDH16A1 ENSG00000161618 19 49956426 49974305 +
CTD-3148I10.9 ENSG00000269469 19 49966009 49989488 +
FLT3LG ENSG00000090554 19 49977464 49990894 +
RPL13A ENSG00000142541 19 49990811 49995565 +
RPS11 ENSG00000142534 19 49999622 50002946 + hsa-mir-150 ENSG00000268000 19 50003781 50004614 +
FCGRT ENSG00000104870 19 50010073 50029590 +
RCN3 ENSG00000142552 19 50030875 50050219 +
NOSIP ENSG00000142546 19 50058968 50093519 -
PRRG2 ENSG00000126460 19 50083903 50094272 +
PRR12 ENSG00000126464 19 50094900 50129696 +
Gene symbol Ensembl ID Chromosome Start End Strand
RRAS ENSG00000126458 19 50138549 50143458 -
SCAF1 ENSG00000126461 19 50145382 50161899 +
IRF3 ENSG00000126456 19 50162826 50169132 -
BCL2L12 ENSG00000126453 19 50168823 50177173 +
PRM 1 ENSG00000126457 19 50179043 50192286 +
ADM5 ENSG00000224420 19 50191921 50193832 +
CPT1C ENSG00000169169 19 50194155 50216988 +
TSKS ENSG00000126467 19 50243010 50266587 -
AP2A1 ENSG00000196961 19 50270225 50310370 +
FUZ ENSG00000010361 19 50310126 50320633 -
MED25 ENSG00000104973 19 50321539 50342073 +
PTOV1 ENSG00000104960 19 50353992 50364001 +
PNKP ENSG00000039650 19 50364461 50371166 -
AKT1S1 ENSG00000204673 19 50372295 50381716 -
TBC1D17 ENSG00000104946 19 50380682 50392005 +
IL4I1 ENSG00000104951 19 50392911 50432796 -
NUP62 ENSG00000213024 19 50410082 50433020 -
SIGLECll ENSG00000269179 19 50412758 50461648 -
ATF5 ENSG00000169136 19 50431959 50437192 +
SIGLECll ENSG00000161640 19 50452242 50464429 -
VRK3 ENSG00000105053 19 50479724 50529203 -
ZNF473 ENSG00000142528 19 50528971 50556671 +
IZUM02 ENSG00000161652 19 50655805 50666452 -
MYH14 ENSG00000105357 19 50691443 50813802 +
KCNC3 ENSG00000131398 19 50815194 50836772 -
NR1H2 ENSG00000131408 19 50832910 50886239 +
NAPSA ENSG00000131400 19 50861734 50869087 -
POLD1 ENSG00000062822 19 50887461 50921273 +
SPIB ENSG00000142539 19 50919056 50931844 +
SPIB ENSG00000269404 19 50922195 50934570 +
MYBPC2 ENSG00000086967 19 50936160 50969578 +
FAM71E1 ENSG00000142530 19 50970042 50980010 -
EMC10 ENSG00000161671 19 50979657 50986608 +
JOSD2 ENSG00000161677 19 51009255 51014610 -
ASPDH ENSG00000204653 19 51014857 51017947 -
LRRC4B ENSG00000131409 19 51020149 51071302 -
SYT3 ENSG00000213023 19 51124564 51171651 -
C19orf81 ENSG00000235034 19 51152702 51162567 +
SHANK1 ENSG00000161681 19 51165084 51222707 -
CLEC11A ENSG00000105472 19 51226586 51228974 +
GPR32 ENSG00000142511 19 51273721 51274989 +
ACPT ENSG00000142513 19 51293672 51298481 +
C19orf48 ENSG00000167747 19 51300961 51308186 -
Gene symbol Ensembl ID Chromosome Start End Strand
KLK1 ENSG00000167748 19 51322404 51327043 -
KLK15 ENSG00000174562 19 51328545 51340469 -
KLK3 ENSG00000142515 19 51358171 51364020 +
KLK2 ENSG00000167751 19 51364824 51383823 +
AC037199.1 ENSG00000267880 19 51377552 51378040 -
KLK4 ENSG00000167749 19 51409608 51413994 -
KLK5 ENSG00000167754 19 51446559 51456349 -
KLK6 ENSG00000167755 19 51461887 51472929 -
KLK7 ENSG00000169035 19 51479729 51487355 -
KLK8 ENSG00000129455 19 51499263 51505967 -
KLK9 ENSG00000269741 19 51499274 51512837 -
KLK9 ENSG00000213022 19 51503806 51512890 -
KLK10 ENSG00000129451 19 51515995 51523431 -
KLK11 ENSG00000167757 19 51525472 51531295 -
KLK12 ENSG00000186474 19 51532348 51538486 -
KLK13 ENSG00000167759 19 51559463 51568371 -
KLK14 ENSG00000129437 19 51580574 51587502 -
CTU1 ENSG00000142544 19 51600863 51611627 -
SIGLEC9 ENSG00000129450 19 51628165 51639908 +
SIGLEC7 ENSG00000168995 19 51645556 51656783 +
CD33 ENSG00000105383 19 51728320 51747115 +
SIGLECLl ENSG00000179213 19 51749603 51772584 +
IGLON5 ENSG00000142549 19 51815102 51833608 +
VSIG10L ENSG00000186806 19 51834790 51845378 -
ETFB ENSG00000105379 19 51848423 51869672 -
CTD- ENSG00000269403 19 51853627 51871353 —
2616J11.11
CLDND2 ENSG00000160318 19 51870352 51872257 -
NKG7 ENSG00000105374 19 51874860 51875969 -
LIM2 ENSG00000105370 19 51883163 51891214 -
CTD-2616J11.4 ENSG00000262874 19 51891543 51893828 -
SIGLEC10 ENSG00000142512 19 51913275 51921057 -
SIGLEC8 ENSG00000105366 19 51954101 51961710 -
CEACAM18 ENSG00000213822 19 51979838 51986611 +
SIGLEC12 ENSG00000254521 19 51994611 52005043 -
SIGLEC6 ENSG00000105492 19 52022779 52035110 -
ZNF175 ENSG00000105497 19 52074551 52092991 +
AC018755.11 ENSG00000167765 19 52095036 52097633 -
SIGLEC5 ENSG00000105501 19 52114781 52150151 -
SIGLEC5 ENSG00000268500 19 52115344 52150142 -
SIGLEC14 ENSG00000254415 19 52145823 52150054 -
HAS1 ENSG00000105509 19 52216365 52227247 -
FPR1 ENSG00000171051 19 52248425 52307363 -
FPR2 ENSG00000171049 19 52255279 52273760 +
Gene symbol Ensembl ID Chromosome Start End Strand
FPR3 ENSG00000187474 19 52298416 52329442 +
ZNF577 ENSG00000161551 19 52359055 52394203 -
ZNF649 ENSG00000198093 19 52392477 52408293 -
ZNF613 ENSG00000176024 19 52430400 52452012 +
ZNF350 ENSG00000256683 19 52467596 52490109 -
ZNF615 ENSG00000197619 19 52494585 52511483 -
ZNF614 ENSG00000142556 19 52516018 52533493 -
ZNF432 ENSG00000256087 19 52534632 52598991 -
ZNF841 ENSG00000197608 19 52567719 52599018 -
ZNF616 ENSG00000204611 19 52616344 52643175 -
ZNF836 ENSG00000196267 19 52657117 52674896 -
PPP2R1A ENSG00000105568 19 52693292 52730687 +
ZNF766 ENSG00000196214 19 52772824 52795977 +
ZNF480 ENSG00000198464 19 52800430 52829175 +
ZNF610 ENSG00000167554 19 52839498 52871031 +
ZNF880 ENSG00000221923 19 52873170 52889048 +
ZNF528 ENSG00000167555 19 52901102 52921665 +
ZNF534 ENSG00000198633 19 52932440 52955568 +
ZNF578 ENSG00000258405 19 52956829 53015407 +
ZNF808 ENSG00000198482 19 53030905 53067717 +
ZNF701 ENSG00000167562 19 53059075 53090427 +
ZNF83 ENSG00000167766 19 53097313 53193749 -
ZNF611 ENSG00000213020 19 53206066 53238326 -
ZNF600 ENSG00000189190 19 53267448 53290044 -
ZNF28 ENSG00000198538 19 53300662 53360853 -
ZNF468 ENSG00000204604 19 53341261 53360902 -
ZNF320 ENSG00000182986 19 53367043 53400946 -
ZNF816 ENSG00000180257 19 53430388 53466164 -
ZNF321P ENSG00000221874 19 53431728 53466076 -
ERW-1 ENSG00000269526 19 53517174 53519375 +
ERW-2 ENSG00000268964 19 53547991 53554329 +
ZNF160 ENSG00000170949 19 53569859 53606689 -
ZNF415 ENSG00000170954 19 53611132 53636330 -
ZNF347 ENSG00000197937 19 53627325 53662328 -
ZNF665 ENSG00000197497 19 53662466 53696639 -
ZNF677 ENSG00000197928 19 53731577 53758151 -
VN1R2 ENSG00000196131 19 53761545 53765090 +
VN1R4 ENSG00000228567 19 53769929 53770972 -
BIRC8 ENSG00000163098 19 53792856 53794875 -
ZNF845 ENSG00000213799 19 53837002 53858122 +
ZNF525 ENSG00000203326 19 53868946 53895470 +
ZNF765 ENSG00000196417 19 53893046 53930574 +
ZNF813 ENSG00000198346 19 53970989 54006950 +
Gene symbol Ensembl ID Chromosome Start End Strand
ZNF331 ENSG00000130844 19 54024235 54083523 +
CTB-167G5.5 ENSG00000268864 19 54102882 54106751 -
DPRX ENSG00000204595 19 54135310 54140263 +
NLRP12 ENSG00000142405 19 54296857 54327648 -
MYADM ENSG00000179820 19 54369477 54379691 +
PRKCG ENSG00000126583 19 54382444 54410906 +
CACNG7 ENSG00000105605 19 54412589 54447195 +
CACNG8 ENSG00000142408 19 54466294 54493469 +
CACNG6 ENSG00000130433 19 54495542 54515923 +
VSTM1 ENSG00000189068 19 54544079 54567207 - ARM1 ENSG00000248385 19 54573149 54584634 -
OSCAR ENSG00000170909 19 54597933 54606000 -
NDUFA3 ENSG00000170906 19 54606036 54614898 +
TFPT ENSG00000105619 19 54610320 54619055 -
PRPF31 ENSG00000105618 19 54618837 54635140 +
CNOT3 ENSG00000088038 19 54641444 54659419 +
LENG1 ENSG00000105617 19 54658899 54663620 -
TMC4 ENSG00000167608 19 54663846 54676944 -
MBOA 7 ENSG00000125505 19 54677107 54693733 -
TSEN34 ENSG00000170892 19 54693789 54697585 +
RPS9 ENSG00000170889 19 54704610 54752862 +
LILRB3 ENSG00000204577 19 54720147 54746602 -
LILRA6 ENSG00000244482 19 54720737 54747130 -
LILRB5 ENSG00000105609 19 54754263 54761167 -
LILRB2 ENSG00000131042 19 54777675 54785039 -
LILRA3 ENSG00000170866 19 54799854 54809952 -
LILRA5 ENSG00000187116 19 54818353 54824409 -
LILRA4 ENSG00000239961 19 54844456 54850421 -
LAIR1 ENSG00000167613 19 54865262 54882165 -
TTYH1 ENSG00000167614 19 54926373 54948080 +
LENG8 ENSG00000167615 19 54960065 54973217 +
LENG9 ENSG00000182909 19 54972981 54974894 -
CDC42EP5 ENSG00000167617 19 54976210 54984411 -
LAIR2 ENSG00000167618 19 55009100 55021897 +
KIR3DX1 ENSG00000104970 19 55043909 55057053 +
LILRA2 ENSG00000239998 19 55084387 55099027 +
LILRB1 ENSG00000104972 19 55085346 55148979 +
LILRAl ENSG00000104974 19 55105047 55113555 +
AC009892.10 ENSG00000224730 19 55147173 55150343 -
LILRB4 ENSG00000186818 19 55155340 55181810 +
KIR3DL1 ENSG00000167633 19 55235969 55378448 +
KIR3DL3 ENSG00000242019 19 55235984 55248003 +
KIR2DL4 ENSG00000189013 19 55236002 55325972 +
Gene symbol Ensembl ID Chromosome Start End Strand
KIR2DL3 ENSG00000243772 19 55249980 55295776 +
KIR2DL1 ENSG00000125498 19 55281263 55295774 +
KIR3DL2 ENSG00000240403 19 55361898 55378662 +
FCAR ENSG00000186431 19 55385549 55401838 +
NCR1 ENSG00000189430 19 55417508 55427508 +
NLRP7 ENSG00000167634 19 55434877 55477680 -
NLRP2 ENSG00000022556 19 55464498 55512510 +
GP6 ENSG00000088053 19 55525073 55549632 -
CTC-550B14.6 ENSG00000267149 19 55538961 55565296 -
RDH13 ENSG00000160439 19 55550476 55582659 -
EPS8L1 ENSG00000131037 19 55583388 55599291 +
PPP1R12C ENSG00000125503 19 55602282 55628927 -
TNN 1 ENSG00000105048 19 55644162 55660722 -
TNNI3 ENSG00000129991 19 55663137 55669141 -
CTD-2587H24.4 ENSG00000267110 19 55666125 55672039 -
DNAAF3 ENSG00000167646 19 55670031 55678090 -
SYT5 ENSG00000129990 19 55682567 55691809 -
PTPRH ENSG00000080031 19 55692616 55720874 -
TMEM86B ENSG00000180089 19 55738007 55741647 -
AC010327.2 ENSG00000269808 19 55738587 55741647 +
PPP6R1 ENSG00000105063 19 55741148 55770363 -
HSPBP1 ENSG00000133265 19 55773599 55791749 -
BRSK1 ENSG00000160469 19 55793440 55823901 +
TMEM150B ENSG00000180061 19 55824169 55845416 -
SUV420H2 ENSG00000133247 19 55851221 55859488 +
SUV420H2 ENSG00000267531 19 55851254 55856561 +
COX6B2 ENSG00000160471 19 55860674 55866182 -
CTD-2105E13.6 ENSG00000267706 19 55863679 55870884 -
FAM71E2 ENSG00000180043 19 55866276 55874620 -
IL11 ENSG00000095752 19 55875757 55881831 -
TMEM190 ENSG00000160472 19 55888204 55889612 +
TMEM238 ENSG00000233493 19 55890613 55895966 -
RPL28 ENSG00000108107 19 55896713 55914612 +
UBE2S ENSG00000108106 19 55912652 55919145 -
SHISA7 ENSG00000187902 19 55940107 55954230 -
ISOC2 ENSG00000063241 19 55964352 55973710 -
ZNF628 ENSG00000197483 19 55987699 55995854 +
NAT14 ENSG00000090971 19 55996371 55998935 +
SSC5D ENSG00000179954 19 55999771 56030465 +
SBK2 ENSG00000187550 19 56041100 56048456 -
SGK110 ENSG00000231274 19 56052023 56056909 -
ZNF579 ENSG00000218891 19 56088899 56092211 -
FIZ1 ENSG00000179943 19 56102746 56113336 -
Gene symbol Ensembl ID Chromosome Start End Strand
ZNF524 ENSG00000171443 19 56111388 56114504 +
ZNF865 ENSG00000261221 19 56116771 56128635 +
ZNF784 ENSG00000179922 19 56132108 56135967 -
ZNF580 ENSG00000213015 19 56146382 56154835 +
ZNF581 ENSG00000171425 19 56146825 56156988 +
CCDC106 ENSG00000173581 19 56152428 56164527 +
U2AF2 ENSG00000063244 19 56165512 56186081 +
EPN1 ENSG00000063245 19 56186592 56221224 +
NLRP9 ENSG00000185792 19 56219798 56249768 -
RFPL4A ENSG00000223638 19 56270380 56274541 +
CTD-2611012.2 ENSG00000229292 19 56280507 56284545 +
NLRP11 ENSG00000179873 19 56296770 56348166 -
NLRP4 ENSG00000160505 19 56347944 56393220 +
NLRP13 ENSG00000173572 19 56403065 56443702 -
NLRP8 ENSG00000179709 19 56459198 56499995 +
NLRP5 ENSG00000171487 19 56511092 56573179 +
ZNF787 ENSG00000142409 19 56598732 56632649 -
ZNF444 ENSG00000167685 19 56643968 56672262 +
AC024580.1 ENSG00000204533 19 56662314 56663250 -
GALP ENSG00000197487 19 56687389 56697144 +
ZSCAN5B ENSG00000197213 19 56700939 56709289 -
ZSCAN5C ENSG00000204532 19 56713670 56720821 +
ZSCAN5A ENSG00000131848 19 56732681 56879752 -
ZSCAN5D ENSG00000267908 19 56751773 56758863 +
AC006116.20 ENSG00000267710 19 56784138 56821819 +
ZNF582 ENSG00000018869 19 56887413 56904914 -
ZNF583 ENSG00000198440 19 56909335 56947404 +
ZNF667 ENSG00000198046 19 56950694 56989434 -
ZNF471 ENSG00000196263 19 57019212 57041590 +
ZFP28 ENSG00000196867 19 57050317 57068169 +
ZNF470 ENSG00000197016 19 57078880 57100279 +
SEGMENT-11
FBXL7 ENSG00000183580 5 15500305 15939900 +
MARCH11 ENSG00000183654 5 16067248 16180871 -
ZNF622 ENSG00000173545 5 16451628 16465901 -
FAM134B ENSG00000154153 5 16473147 16617167 -
MYO10 ENSG00000145555 5 16665395 16936372 -
PRDM9 ENSG00000164256 5 23507264 23528706 +
C5orfl7 ENSG00000248874 5 23951457 24178372 +
CDH10 ENSG00000040731 5 24487209 24645087 -
CDH9 ENSG00000113100 5 26880709 27121257 -
CDH6 ENSG00000113361 5 31193857 31329253 +
DROSHA ENSG00000113360 5 31400604 31532303 -
Gene symbol Ensembl ID Chromosome Start End Strand
C5orf22 ENSG00000082213 5 31532373 31555165 +
PDZD2 ENSG00000133401 5 31639517 32111037 +
G0LPH3 ENSG00000113384 5 32124810 32174456 -
MTMR12 ENSG00000150712 5 32227100 32313115 -
ZFR ENSG00000056097 5 32354456 32444867 -
SUB1 ENSG00000113387 5 32531739 32604185 +
NPR3 ENSG00000113389 5 32689176 32791819 +
AC026703.1 ENSG00000181495 5 32788945 32791819 +
TARS ENSG00000113407 5 33440802 33469644 +
ADAMTS12 ENSG00000151388 5 33523640 33892297 -
RXFP3 ENSG00000182631 5 33936491 33939023 +
SLC45A2 ENSG00000164175 5 33944721 33984835 -
AMACR ENSG00000242110 5 33986283 34008220 -
C1QTNF3 ENSG00000082196 5 33987279 34124633 -
RAI14 ENSG00000039560 5 34656342 34832732 +
TTC23L ENSG00000205838 5 34838938 34899561 +
RADl ENSG00000113456 5 34905369 34919094 -
BRIX1 ENSG00000113460 5 34915481 34926101 +
DNAJC21 ENSG00000168724 5 34929698 34959069 +
AGX 2 ENSG00000113492 5 34998206 35048198 -
PRLR ENSG00000113494 5 35048861 35230794 -
AC010368.2 ENSG00000269027 5 35051012 35051198 +
SPEF2 ENSG00000152582 5 35617946 35814713 +
IL7R ENSG00000168685 5 35852797 35879705 +
CAPSL ENSG00000152611 5 35904397 35938881 -
UGT3A1 ENSG00000145626 5 35951112 36001130 -
UGT3A2 ENSG00000168671 5 36035119 36071460 -
LMBRD2 ENSG00000164187 5 36098514 36152063 -
SKP2 ENSG00000145604 5 36152091 36184421 +
NADKD1 ENSG00000152620 5 36192694 36242381 -
RANBP3L ENSG00000164188 5 36248536 36302216 -
SLC1A3 ENSG00000079215 5 36606457 36688436 +
NIPBL ENSG00000164190 5 36876861 37066515 +
C5orf42 ENSG00000197603 5 37106330 37249530 -
NUP155 ENSG00000113569 5 37288239 37371283 -
WDR70 ENSG00000082068 5 37379314 37753537 +
GDNF ENSG00000168621 5 37812779 37839788 -
EGFLAM ENSG00000164318 5 38258511 38465123 +
LIFR ENSG00000113594 5 38475065 38608456 -
AC091435.1 ENSG00000205783 5 38819804 38821581 -
AC091435.2 ENSG00000205785 5 38820766 38823298 +
OSMR ENSG00000145623 5 38845960 38945698 +
RICTOR ENSG00000164327 5 38938021 39074510 -
Gene symbol Ensembl ID Chromosome Start End Strand
FYB ENSG00000082074 5 39105338 39274630 -
AC008964.1 ENSG00000269215 5 39105358 39107350 +
C9 ENSG00000113600 5 39284364 39424970 -
DAB2 ENSG00000153071 5 39371780 39462402 -
PTGER4 ENSG00000171522 5 40679600 40693837 +
TTC33 ENSG00000113638 5 40714577 40756077 -
PRKAA1 ENSG00000132356 5 40759481 40798476 -
RPL37 ENSG00000145592 5 40825364 40835437 -
CARD6 ENSG00000132357 5 40841286 40860275 +
C7 ENSG00000112936 5 40909354 40983041 +
HEATR7B2 ENSG00000171495 5 40998119 41071444 -
C6 ENSG00000039537 5 41142336 41261540 -
PLCXD3 ENSG00000182836 5 41307056 41510730 -
OXCT1 ENSG00000083720 5 41730167 41870621 -
C5orf51 ENSG00000205765 5 41904290 41921738 +
FBX04 ENSG00000151876 5 41925356 41941845 +
GHR ENSG00000112964 5 42423879 42721979 +
CCDC152 ENSG00000198865 5 42756903 42802462 +
SEPP1 ENSG00000250722 5 42799982 42887494 -
ANXA2R ENSG00000177721 5 43039335 43043272 -
ZNF131 ENSG00000172262 5 43065278 43192123 +
NIM1 ENSG00000177453 5 43192173 43280952 +
HMGCS1 ENSG00000112972 5 43289497 43313614 -
CCL28 ENSG00000151882 5 43376747 43412493 -
C5orf28 ENSG00000151881 5 43444354 43483995 -
C5orf34 ENSG00000172244 5 43486803 43515247 -
PAIP1 ENSG00000172239 5 43526369 43557860 -
NNT ENSG00000112992 5 43602795 43707507 +
FGF10 ENSG00000070193 5 44303646 44389808 -
MRPS30 ENSG00000112996 5 44809027 44820530 +
SEGMENT-12
CCDC171 ENSG00000164989 9 15552895 16061661 +
CNTLN ENSG00000044459 9 17134980 17503921 +
SEGMENT-13
SNURF ENSG00000214265 15 25200133 25245423 +
UBE3A ENSG00000114062 15 25582381 25684128 -
ATP10A ENSG00000206190 15 25922420 26110317 -
GABRB3 ENSG00000166206 15 26788693 27184686 -
GABRA5 ENSG00000186297 15 27111510 27194354 +
GABRG3 ENSG00000182256 15 27216429 27778373 +
RYR3 ENSG00000198838 15 33603163 34158303 +
AVEN ENSG00000169857 15 34158428 34331377 -
CHRM5 ENSG00000184984 15 34260921 34357291 +
Gene symbol Ensembl ID Chromosome Start End Strand
EMC7 ENSG00000134153 15 34376218 34394149 -
PGBD4 ENSG00000182405 15 34394274 34396591 +
KATNBL1 ENSG00000134152 15 34432875 34502297 -
EMC4 ENSG00000128463 15 34517200 34522357 +
GJD2 ENSG00000159248 15 35043233 35047166 -
ACTC1 ENSG00000159251 15 35080297 35088340 -
AQR ENSG00000021776 15 35147732 35262040 -
ZNF770 ENSG00000198146 15 35270542 35280488 -
AC114546.1 ENSG00000212768 15 35270552 35272268 +
ATPBD4 ENSG00000134146 15 35509546 35838394 -
C15orf41 ENSG00000186073 15 36871812 37102449 +
MEIS2 ENSG00000134138 15 37181409 37393504 -
TMC05A ENSG00000166069 15 38214140 38259925 +
SPRED1 ENSG00000166068 15 38544527 38649450 +
FAM98B ENSG00000171262 15 38746328 38779911 +
RASGRP1 ENSG00000172575 15 38780304 38857776 -
C15orf53 ENSG00000175779 15 38988799 38992239 +
C15orf54 ENSG00000175746 15 39542885 39547046 +
THBS1 ENSG00000137801 15 39873280 39891667 +
FSIP1 ENSG00000150667 15 39892232 40075031 -
GPR176 ENSG00000166073 15 40091233 40213093 -
EIF2AK4 ENSG00000128829 15 40226347 40327797 +
SRP14 ENSG00000140319 15 40327940 40331389 -
BMF ENSG00000104081 15 40380091 40401093 -
BUB1B ENSG00000156970 15 40453224 40513337 +
RP11-133K1.2 ENSG00000259288 15 40509629 40568597 +
PAK6 ENSG00000137843 15 40509629 40569688 +
C15orf56 ENSG00000176753 15 40542865 40545170 -
PLCB2 ENSG00000137841 15 40570377 40600136 -
ANKRD63 ENSG00000230778 15 40573645 40574787 -
C15orf52 ENSG00000188549 15 40623653 40633168 -
PHGR1 ENSG00000233041 15 40643234 40648635 +
DISP2 ENSG00000140323 15 40650436 40663257 +
C15orf23 ENSG00000128944 15 40674922 40686446 +
IVD ENSG00000128928 15 40697686 40728146 +
BAHD1 ENSG00000140320 15 40731920 40760441 +
CHST14 ENSG00000169105 15 40763160 40765353 +
C15orf57 ENSG00000128891 15 40820882 40857256 -
RPUSD2 ENSG00000166133 15 40861499 40866659 +
CASC5 ENSG00000137812 15 40886218 40956540 +
FAM82A2 ENSG00000137824 15 41028082 41048049 -
GCHFR ENSG00000137880 15 41056218 41059906 +
DNAJC17 ENSG00000104129 15 41060067 41099675 -
Gene symbol Ensembl ID Chromosome Start End Strand
C15orf62 ENSG00000188277 15 41062159 41064647 +
ZFYVE19 ENSG00000166140 15 41099284 41106767 +
PPP1R14D ENSG00000166143 15 41107650 41120907 -
SPINT1 ENSG00000166145 15 41136216 41150405 +
RHOV ENSG00000104140 15 41164412 41166487 -
VPS18 ENSG00000104142 15 41186628 41196173 +
DLL4 ENSG00000128917 15 41221538 41231237 +
CHAC1 ENSG00000128965 15 41245160 41248710 +
INO80 ENSG00000128908 15 41271078 41408552 -
EXD1 ENSG00000178997 15 41474923 41522941 -
CHP1 ENSG00000187446 15 41523037 41574043 +
OIP5 ENSG00000104147 15 41601466 41624819 -
NUSAP1 ENSG00000137804 15 41624892 41673248 +
NDUFAF1 ENSG00000137806 15 41679551 41694717 -
RTF1 ENSG00000137815 15 41700606 41775761 +
I PKA ENSG00000137825 15 41785591 41795747 +
LTK ENSG00000062524 15 41795836 41806085 -
RPAP1 ENSG00000103932 15 41809374 41836467 -
CAPN3 ENSG00000092529 15 42640301 42704516 +
ZFP106 ENSG00000103994 15 42705021 42783321 -
SNAP23 ENSG00000092531 15 42783431 42837547 +
LRRC57 ENSG00000180979 15 42834720 42841000 -
HAUS2 ENSG00000137814 15 42841008 42862192 +
STARD9 ENSG00000159433 15 42867857 43013179 +
CDAN1 ENSG00000140326 15 43015757 43029324 -
TTBK2 ENSG00000128881 15 43030932 43213007 -
CASC4 ENSG00000166734 15 44580927 44707956 +
CTDSPL2 ENSG00000137770 15 44719432 44821236 +
EIF3J ENSG00000104131 15 44829255 44855227 +
SPG11 ENSG00000104133 15 44854894 44955876 -
PA L2 ENSG00000229474 15 44957930 45003514 -
B2M ENSG00000166710 15 45003675 45011075 +
TRIM69 ENSG00000185880 15 45021186 45060027 +
C15orf43 ENSG00000167014 15 45248900 45271427 +
SORD ENSG00000140263 15 45315302 45369383 +
DUOX2 ENSG00000140279 15 45384848 45406542 -
DUOXA2 ENSG00000140274 15 45406519 45410619 +
DUOXA1 ENSG00000140254 15 45409569 45422136 -
DUOX1 ENSG00000137857 15 45422131 45457774 +
SHF ENSG00000138606 15 45459412 45493373 -
SLC28A2 ENSG00000137860 15 45544428 45568149 +
GATM ENSG00000171766 15 45653322 45694416 -
SPA A5L1 ENSG00000171763 15 45694529 45713617 +
Gene symbol Ensembl ID Chromosome Start End Strand
C15orf48 ENSG00000166920 15 45722727 45740959 +
SLC30A4 ENSG00000104154 15 45771809 45815005 -
BL0C1S6 ENSG00000104164 15 45879321 45908197 +
SQRDL ENSG00000260170 15 45879549 45968512 +
SQRDL ENSG00000137767 15 45923346 45983492 +
FKSG62 ENSG00000259752 15 47425693 47426320 -
WDR61 ENSG00000140395 15 78570177 78592136 -
CRABPI ENSG00000166426 15 78632666 78640572 +
IREB2 ENSG00000136381 15 78729773 78793798 +
AGPHD1 ENSG00000188266 15 78799906 78829714 +
AC027228.1 ENSG00000268838 15 78830023 78831288 +
PSMA4 ENSG00000041357 15 78832747 78841604 +
CHRNA5 ENSG00000169684 15 78857862 78887611 +
CHRNA3 ENSG00000080644 15 78885394 78913637 -
CHRNB4 ENSG00000117971 15 78916461 79012628 -
ADAMTS7 ENSG00000136378 15 79051545 79103773 -
MORF4L1 ENSG00000185787 15 79102829 79190475 +
CTSH ENSG00000103811 15 79213400 79241916 -
RASGRFl ENSG00000058335 15 79252289 79383115 -
ANKRD34C ENSG00000235711 15 79575146 79590580 +
TMED3 ENSG00000166557 15 79603404 79704334 +
KIAA1024 ENSG00000169330 15 79724858 79764632 +
MTHFS ENSG00000136371 15 80125927 80189721 -
ST20-MTHFS ENSG00000259332 15 80137537 80216096 -
ST20 ENSG00000180953 15 80191182 80216044 -
C15orf37 ENSG00000259642 15 80215113 80217194 +
C150RF37 ENSG00000257028 15 80215507 80217194 +
BCL2A1 ENSG00000140379 15 80253231 80263788 -
ZFAND6 ENSG00000086666 15 80351910 80430735 +
FAH ENSG00000103876 15 80444832 80479288 +
RP11-210M15.2 ENSG00000259495 15 80637195 80695917 -
ARN 2 ENSG00000172379 15 80696692 80890278 +
FAM108C1 ENSG00000136379 15 80972025 81047962 +
KIAA1199 ENSG00000103888 15 81071684 81244117 +
RP11-351M8.1 ENSG00000259649 15 81188532 81202118 -
MESDC2 ENSG00000117899 15 81239667 81282219 -
MESDC1 ENSG00000140406 15 81293295 81296342 +
C15orf26 ENSG00000156206 15 81299374 81441516 +
IL16 ENSG00000172349 15 81451916 81605104 +
STARD5 ENSG00000172345 15 81601394 81616524 -
TMC3 ENSG00000188869 15 81623558 81666554 -
MEX3B ENSG00000183496 15 82334119 82338482 -
RP11-597K23.2 ENSG00000259518 15 82380935 82390035 +
Gene symbol Ensembl ID Chromosome Start End Strand
AP3B2 ENSG00000103723 15 83328033 83378666 -
FSD2 ENSG00000186628 15 83424114 83474822 -
WHAMM ENSG00000156232 15 83478380 83503611 +
H0MER2 ENSG00000103942 15 83509838 83654661 -
FAM103A1 ENSG00000169612 15 83654959 83659809 +
C15orf40 ENSG00000169609 15 83657193 83680393 -
BTBD1 ENSG00000064726 15 83685174 83736106 -
TM6SF1 ENSG00000136404 15 83776159 83813606 +
HDGFRP3 ENSG00000166503 15 83784320 83876770 -
BNC1 ENSG00000169594 15 83924655 83953466 -
KLHL25 ENSG00000183655 15 86302554 86338261 -
AGBL1 ENSG00000166748 15 86685227 87572283 +
ZNF710 ENSG00000140548 15 90544624 90625438 +
IDH2 ENSG00000182054 15 90626277 90645736 -
SEMA4B ENSG00000185033 15 90703836 90772911 +
CIB1 ENSG00000185043 15 90773207 90777279 -
GDPGP1 ENSG00000183208 15 90777040 90785315 +
TTLL13 ENSG00000213471 15 90792762 90808199 +
RP11-697E2.6 ENSG00000261147 15 90792788 90815440 +
NGRN ENSG00000182768 15 90808891 90816463 +
GABARAPL3 ENSG00000238244 15 90890819 90892669 -
ZNF774 ENSG00000196391 15 90895477 90909324 +
IQGAP1 ENSG00000140575 15 90931450 91045475 +
CRTC3 ENSG00000140577 15 91073157 91188577 +
BLM ENSG00000197299 15 91260558 91358859 +
FURIN ENSG00000140564 15 91411822 91426688 +
FES ENSG00000182511 15 91426925 91439006 +
MAN2A2 ENSG00000196547 15 91445448 91465814 +
UNC45A ENSG00000140553 15 91471728 91497323 +
HDDC3 ENSG00000184508 15 91474148 91475799 -
RCCD1 ENSG00000166965 15 91498100 91506349 +
PRC1 ENSG00000198901 15 91509270 91538859 -
VPS33B ENSG00000184056 15 91541646 91565833 -
SV2B ENSG00000185518 15 91643180 91844539 +
FAM174B ENSG00000185442 15 93160673 93353114 -
CHD2 ENSG00000173575 15 93425937 93571237 +
RGMA ENSG00000182175 15 93586636 93632433 -
AC112693.2 ENSG00000269360 15 93749295 93751277 +
MCTP2 ENSG00000140563 15 94774767 95023632 +
AC016251.1 ENSG00000205148 15 96831280 96831660 -
NR2F2 ENSG00000185551 15 96869167 96883492 +
AC087477.1 ENSG00000268484 15 96904487 96904900 +
SPATA8 ENSG00000185594 15 97326619 97328845 +
Gene symbol Ensembl ID Chromosome Start End Strand
RP11-82I10.1 ENSG00000251209 15 98285448 98417780 -
ARRDC4 ENSG00000140450 15 98462784 98517068 +
PGPEP1L ENSG00000183571 15 99511459 99551024 -
SYNM ENSG00000182253 15 99638420 99675798 +
TTC23 ENSG00000103852 15 99676528 99791428 -
LRRC28 ENSG00000168904 15 99791567 99930934 +
AC022819.4 ENSG00000268730 15 99859300 99859828 -
MEF2A ENSG00000068305 15 100017370 100256671 +
AC015660.1 ENSG00000269810 15 100038447 100038578 -
LYSMD4 ENSG00000183060 15 100255906 100273766 -
DKFZP779J2370 ENSG00000214397 15 100255908 100258029 -
CTD-2054N24.2 ENSG00000259363 15 100347228 100417353 +
ADAMTS17 ENSG00000140470 15 100511794 100882210 -
SEGMENT-14
USP25 ENSG00000155313 21 17102344 17252377 +
C21orf37 ENSG00000232560 21 18811208 18821503 +
CXADR ENSG00000154639 21 18884700 18965897 +
BTG3 ENSG00000154640 21 18965971 18985265 -
C21orf91 ENSG00000154642 21 19161284 19191703 -
CHODL ENSG00000154645 21 19273580 19639690 +
KR AP19-1 ENSG00000184351 21 31852018 31852663 -
KR AP19-2 ENSG00000186965 21 31859362 31859755 -
KRTAP19-3 ENSG00000244025 21 31863782 31864275 -
KR AP19-4 ENSG00000186967 21 31869142 31869451 -
KR AP19-5 ENSG00000186977 21 31873975 31874435 -
KRTAP19-6 ENSG00000186925 21 31913854 31914183 -
KR AP19-7 ENSG00000244362 21 31933194 31933633 -
KRTAP22-2 ENSG00000206106 21 31962424 31962716 -
KRTAP6-3 ENSG00000212938 21 31964759 31965394 +
KRTAP6-2 ENSG00000186930 21 31970909 31971219 -
KRTAP22-1 ENSG00000186924 21 31973414 31973612 +
KRTAP6-1 ENSG00000184724 21 31985750 31986249 -
KRTAP20-1 ENSG00000244624 21 31988750 31989003 +
KRTAP20-4 ENSG00000206105 21 31992946 31993169 +
KRTAP20-2 ENSG00000184032 21 32007555 32007938 +
KRTAP20-3 ENSG00000206104 21 32015183 32015455 +
KRTAP21-3 ENSG00000231068 21 32090843 32091095 -
KRTAP21-2 ENSG00000187026 21 32119112 32119551 -
KRTAP21-1 ENSG00000187005 21 32127439 32127746 -
KRTAP8-1 ENSG00000183640 21 32185016 32185570 -
KR APll-1 ENSG00000182591 21 32252966 32253874 -
KR AP19-8 ENSG00000206102 21 32410478 32410795 -
SOD1 ENSG00000142168 21 33031935 33041244 +
Gene symbol Ensembl ID Chromosome Start End Strand
SCAF4 ENSG00000156304 21 33043313 33104431 -
HUNK ENSG00000142149 21 33245628 33416946 +
MIS18A ENSG00000159055 21 33640530 33651380 -
MRAP ENSG00000170262 21 33664124 33687095 +
URB1 ENSG00000142207 21 33683329 33765335 -
C21orf119 ENSG00000256073 21 33765439 33766254 +
EVA1C ENSG00000166979 21 33784314 33887707 +
TCP10L ENSG00000242220 21 33948862 33957843 -
C210RF59 ENSG00000265590 21 33949158 33984913 -
C21orf59 ENSG00000159079 21 33964389 33985176 -
SYNJ1 ENSG00000159082 21 34001069 34100359 -
KCNE2 ENSG00000159197 21 35736323 35743440 +
FAM165B ENSG00000205670 21 35747779 35780164 +
AP000322.54 ENSG00000222018 21 35772615 35773370 -
AP000322.53 ENSG00000243627 21 35791013 35796264 -
CLIC6 ENSG00000159212 21 36041688 36090525 +
AP000688.1 ENSG00000268098 21 37402368 37417818 +
SETD4 ENSG00000185917 21 37406839 37451687 -
CBR1 ENSG00000159228 21 37442239 37445464 +
CBR3 ENSG00000159231 21 37507210 37518864 +
DOPEY2 ENSG00000142197 21 37529080 37666572 +
MORC3 ENSG00000159256 21 37692487 37758446 +
CHAF1B ENSG00000159259 21 37757676 37789125 +
CLDN14 ENSG00000159261 21 37832919 37948867 -
AP000695.1 ENSG00000267976 21 37858165 37860058 +
SEGMENT-15
XKR9 ENSG00000221947 8 71581600 71702606 +
GDAP1 ENSG00000104381 8 75233365 75401107 +
RP11-758M4.1 ENSG00000254349 8 75512010 75735548 +
PI15 ENSG00000137558 8 75736772 75767264 +
CRISPLD1 ENSG00000121005 8 75896750 75946793 +
HNF4G ENSG00000164749 8 76320149 76479078 +
PEX2 ENSG00000164751 8 77892494 77913280 -
SEGMENT-16
ZNF626 ENSG00000188171 19 20802867 20844402 -
ZNF66P ENSG00000160229 19 20959110 20991922 +
ZNF98 ENSG00000197360 19 22573821 22715287 -
ZNF492 ENSG00000229676 19 22817126 22850472 +
ZNF99 ENSG00000213973 19 22939007 22966909 -
ZNF730 ENSG00000183850 19 23258012 23332763 +
ZNF724P ENSG00000196081 19 23404401 23433192 -
ZNF91 ENSG00000167232 19 23487793 23578362 -
Table 2 : Physical Location of Segments and Average Copy Number
Segment Chr . GRCh37 Coordinates Length Gene Average Average
(bp) Count copy copy
Start End
number number
Sensiti Refract ve ory
Segment-1 16 53467889 87739290 34271401 264 2 1
Segment-2 18 2537524 76762677 74225153 255 3 2
Segment-3 13 21547171 61148012 39600841 108 2 1
Segment-4 11 77371041 112140678 34769637 155 3 2
Segment-5 4 1873151 187647876 185774725 317 1 2
Segment-6 13 75858808 78338377 2479569 12 3 1
Segment-7 13 78469616 111567416 33097800 50 3 2
Segment-8 16 71315292 72210777 895485 20 3 1
Segment- 9 10 83635070 131982785 48347715 318 2 1
Segment-10 19 47724081 57100279 9376198 335 2 3
Segment-11 5 15500305 44820530 29320225 84 3 2
Segment-12 9 15552895 17503921 1951026 2 3 2
Segment-13 15 25200133 100882210 75682077 194 2 1
Segment-14 21 17102344 37860058 20757714 54 3 2
Segment-15 8 71581600 77913280 6331680 7 3 2
Segment-16 19 20802867 23578362 2775495 8 3 2
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characteristics of circulating tumour cells and circulating tumour microemboli in patients with small-cell lung cancer. J Clin Oncol. 30 (5) , 525-32 (2012) .
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11. Polzer, B., et al. Molecular profiling of single circulating tumour cells with diagnostic intention. EMBO Mol Med. 6(11), 1371-86 (2014) .
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Vincristine (ACO) - a Single Center Experience. J Cancer. 6(11), 1148-54 (2015) .
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All references cited herein are incorporated herein by reference in their entirety and for all purposes to the same extent as if each individual publication or patent or patent application was
specifically and individually indicated to be incorporated by reference in its entirety.
The specific embodiments described herein are offered by way of example, not by way of limitation. Any sub-titles herein are included for convenience only, and are not to be construed as limiting the disclosure in any way.
Claims
1. A method for predicting the response of a subject having small cell lung cancer (SCLC) to chemotherapy, the method comprising:
determining the copy number aberration (CNA) status of at least 10 genomic segments of a circulating tumour cell (CTC) sample obtained from the subject, thereby obtaining a sample CNA profile; and
analysing said sample CNA profile to classify the sample as being chemosensitive or chemorefractory,
wherein said at least 10 genomic segments are selected from the group of genomic segments consisting of:
Segment- 1 : chromosome 16, start : 53467889, end: 87739290;
Segment- 2 : chromosome 18, start : 2537524, end: 76762677
Segment- 3: chromosome 13, start : 21547171, end: 61148012
Segment- 4 : chromosome 11, start : 77371041, end: 112140678
Segment- 5: chromosome 4, start: 1873151, end: 187647876
Segment- 6: chromosome 13, start : 75858808, end: 78338377
Segment- 7 : chromosome 13, start : 78469616, end: 111567416
Segment- 8: chromosome 16, start : 71315292, end: 72210777
Segment- 9: chromosome 10, start : 83635070, end: 131982785
Segment- 10 chromosome 19, start : 47724081, end : 57100279
Segment- 11 chromosome 5, start : 15500305, end: 44820530
Segment- 12 chromosome 9, start : 15552895, end: 17503921
Segment- 13 chromosome 15, start : 25200133, end : 100882210
Segment- 14 chromosome 21, start : 17102344, end : 37860058
Segment- 15 chromosome 8, start : 71581600, end: 77913280
Segment- 16 chromosome 19, start : 20802867, end : 23578362,
wherein said start and end positions are according to the numbering system of Genome Reference Consortium GRCh37, patch release 13, dated 28 June 2013.
2. The method according to claim 1, wherein analysing said sample CNA profile comprises applying a computational classifier to said sample CNA profile, wherein said computational classifier is adapted to assign an unknown CNA profile to the chemosensitive class or the chemorefractory class based on a training set of sample CNA profiles of said at least 10 genomic segments obtained from training samples
of known chemosensitive/chemorefractory status, which training samples include at least two known chemosensitive SCLC CTC samples and at least two known chemorefractory SCLC CTC samples.
3. The method according to claim 2, wherein the computational classifier comprises a support vector machine (SVM) or a partial least squares (PLS) regression.
4. The method according to claim 3, wherein the SVM is a radial basis SVM.
5. The method according to claim 4, wherein the SVM comprises a Gaussian Radial Basis kernel function, and wherein the parameters that support the classifier are as follows:
parameter : cost C = 0.25
Hyperparameter : sigma = 0.0476184222095904
Number of Support Vectors : 43.
6. The method according to claim 1, wherein analysing said sample CNA profile comprises comparing the sample CNA profile with at least one reference CNA profile of said 10 genomic segments, wherein said at least one reference CNA profile comprises:
(iii) a chemosensitive reference CNA profile derived from at least one CTC sample from a chemosensitive SCLC subject; and/or
(iv) a chemorefractory reference CNA profile derived from at least one CTC sample from a chemorefractory SCLC subj ect .
7. The method according to claim 6, wherein said sample CNA profile is compared with both the chemosensitive reference CNA profile and the chemorefractory reference CNA profile and an assessment of best fit is used to classify the sample as being chemosensitive or chemorefractory .
8. The method according to claim 6 or claim 7, wherein the chemosensitive reference CNA profile is an average of at least five CNA profiles each from CTCs of a known chemosensitive SCLC subject.
9. The method according to any one of claims 6 to 8, wherein the chemorefractory reference CNA profile is an average of at least five CNA profiles each from CTCs of a known chemorefractory SCLC subject.
10. The method according to any one of the preceding claims, wherein said at least 10 genomic segments comprise all of the following 16 segments:
Segment- 1 : chromosome 16, start : 53467889, end : 87739290;
Segment- 2 : chromosome 18, start : 2537524, end: 76762677
Segment- 3: chromosome 13, start : 21547171, end: 61148012
Segment- 4 : chromosome 11, start : 77371041, end : 112140678
Segment- 5: chromosome 4, start: 1873151, end: 187647876
Segment- 6: chromosome 13, start : 75858808, end: 78338377
Segment- 7 : chromosome 13, start : 78469616, end : 111567416
Segment- 8 : chromosome 16, start : 71315292, end: 72210777
Segment- 9: chromosome 10, start : 83635070, end : 131982785
Segment- 10 chromosome 19, start : 47724081, end : 57100279
Segment- 11 chromosome 5, start : 15500305, end: 44820530
Segment- 12 chromosome 9, start : 15552895, end: 17503921
Segment- 13 chromosome 15, start : 25200133, end : 100882210
Segment- 14 chromosome 21, start : 17102344, end : 37860058
Segment- 15 chromosome 8, start : 71581600, end: 77913280
Segment- 16 chromosome 19, start : 20802867, end : 23578362,
wherein said start and end positions are according to the numbering system of Genome Reference Consortium GRCh37 patch release 13, dated 28 June 2013.
11. The method according to any one of the preceding claims, wherein determining the CNA status of each genomic segment comprises determining the copy number of at least 50 base pairs of one or more loci within the segment.
12. The method according to claim 11, wherein the genomic segments comprise the following loci:
(i) segment 1: C16orf80, CSNK2A2, CCDC135, KATNB1, KIFC3, CTD- 260009.1, CNGB1, TEPP, ZNF319, USB1, MMP15, NLRC5, CPNE2, FAM192A, RSPRY1, ARL2BP, PLLP, CCL22, CX3CL1, CCL17, CIAPIN1, COQ9, POLR2C, DOK4, CCDC102A, GPR114, GPR97, CETP, GPR56, NUDT21, OGFOD1, BBS2, MT4, MT3, MT2A, MT1E, AC026461.1, MT1M, MT1A, MT1B, MT1F, MT1G, MT1H, MT1X, NUP93, SLC12A3, HERPUD1, CNOT1, AMFR, GNAOl, CES5A, SLC38A7, GOT2, CCDC113, PRSS54, GINS3, NDRG4, SETD6, RP11 -105C20.2 , FTO, LPCAT2, CAPNS2, SLC6A2, CES1, MMP2, IRX3, IRX5, IRX6, RP11- 324D17.1, RPGRIP1L, ZCCHC14, FOXF1 , MTHFSD, FOXC2, FOXL1, C16orf95, JPH3, AC010536.1, FLJ00104, MAP1LC3B, RP11-178L8.4 , FBX031, IRF8, EMC8 , COX4I1, MBTPS1, HSDL1, DNAAF1 , TAF1C, ADAD2, KCNG4 , WFDC1, ATP2C2, KIAA1609, COTL1, KLHL36, USP10, CRISPLD2, ZDHHC7, GINS2, SLC38A8, CDH8, KIAA0513, DYNLRB2 , CDYL2, C16orf74, CMC2 , CENPN, ATMIN, C16orf46, GCSH, PKD1L2, BCMOl, GAN, CMIP, PLCG2 , SDR42E1, HSD17B2, MON1B, SYCE1L, ADAMTS18 , MPHOSPH6, CDH13, HSBP1, MLYCD, NUDT7, VAT1L , NECAB2, RBL2, AKTIP, OSGIN1, CLEC3A, WWOX, PIH1, MAF, GSE1, RP11-58C22.1, FAM92B, RP11 - 680G10.1 , CNTNAP4, CDH11, AGRP, CDH5, THAP11, NUTF2, EDC4, NRN1L, RLTPR, ACD, PARD6A, ENKD1,
C16orf86, GFOD2, CENPT, RANBP10, TSNAXIP1, CTCF, FAM65A, ATP6V0D1, NAE1, RP11-77K12.1, TMEM170A, CHST6, CHST5, ESRP2, PLA2G15, SLC7A6, SLC7A60S, CDH16, PSKH1, CFDP1, RP11- 77K12.7 , CMTM4 , RRAD, CA7, PDP2, NFATC3, DYNC1LI2, FAM96B, CES2, CES3, CES4A, CCDC79, TMEM231, CTRL, CTC-479C5.12, PSMB10, LCAT, SLC12A4, DPEP3, DPEP2, DUS2L, DDX28, GABARAPL2, ADAT1, KARS, RFWD3 , MLKL, FA2H, WDR59, ZNRF1, LDHD, ZFP1, CTRB2, CTRB1, BCAR1 , CMTM3 , PRMT7, TERF2IP, CMTM2 , BEAN1, RP11- 403P17.5, AC025287.1, AC132186.1, TK2, CKLF, CKLF-CMTM1, CMTM1, SMPD3, CDH1, TMC07, HAS3, CHTF8, CHTF8, CIRH1A, SNTB2, VPS4A, RP11- 343C2.3, COG8, PDF, RP11-343C2.8 , COG8, RP11-343C2.7, NIP7, TMED6, TERF2, CYB5B, CDH3, HSD11B2, ZFP90, ZFHX3, C16orf47, ZDHHC1, LRRC36, CBFB, TPPP3, KCTD19, C16orf70, B3GNT9, TRADD, FBXL8, RP11-5A19.5, HSF4, NOL3, KIAA0895L, EXOC3L1, E2F4, ELMO3 , LRRC29, AC040160.1, TMEM208, FHOD1, SLC9A5, and PLEKHG4;
(ii) segment 2: APCDD1 , NAPG, PIEZ02, GNAL, CHMP1B, MPPE1, IMPA2, RBBP8, TMEM241, CABLESI , VAPA, RIOK3, NDUFV2, ANKRD12,
IMPACT, SLMOl, HRH4, SPIRE1, C18orf8, AP005482.1, CEP76, PSMG2,
PTPN2, SEH1L, CEP192, LDLRAD4, NPC1, TTC39C, CABYR, OSBPL1A, ZNF521, AQP4, LAMA3, GATA6, KCTD1, SS18, PSMA8, TAF4B, CHST9, FAM210A, RNMT, MC5R, PTPRM, ARHGAP28 , LAMA1 , LRRC30, RP11-865B13.1, AP001094.1, CTAGE1, CTAGE1, TXNDC2, TWSG1, RALBP1, PPP4R1, RAB31, MYL12A,
MYL12B, TGIF1, ANKRD29, RAB12, SOGA2, C18orf42, MYOM1, CDH2,
L3MBTL4, LPIN2, EMILIN2, ZFP161, DSC2, DSC1, DSC3, SMCHD1, EPB41L3, TMEM200C, DLGAP1, SLC14A1, SIGLEC15, EPG5, PSTPIP2, ATP5A1, HAUS1, C18orf25, RNF165, LOXHD1, ST8SIA5, PIAS2, KATNAL2, TCEB3CL2,
TCEB3CL, TCEB3C, TCEB3B, HDHD2, IER3IP1, IER3IP1, SKOR2 , SMAD2, ZBTB7C, AC091150.1, CTIF, SMAD7 , SETBP1, SLC14A2, KIAA1328, DYM, DSG1, ACAA2, RP11- 886H22.1 , MY05B, CCDC11, MBD1, CXXC1, SKA1, MIB1, C18orf32, RPL17-Cl 80RF32 , RPL17, LIPG, RP11 -595B24.2 , CELF4 , MAPK4, MRO, ME2 , ELAC1, RP11- 729L2.2 , SMAD4 , MEX3C, SLC25A52, PIK3C3, TPGS2, RIT2, DSG4, DSG3, DSG2, TTR, B4GALT6, SYT4, FHOD3, TRAPPC8, RNF125, RNF138, MEP1B, FAM59A, NOL4, DTNA, MAPRE2, ZNF397, ZSCAN30, ZNF24, ZNF396, RP11-322E11.6, INO80C, GALNT1, C18orf21, RPRD1A,
MOCOS, ELP2, SLC39A6, METTL4, NDC80, KLHL14 , AC012123.1, CCDC178, ASXL3, DCC, RP11-4104.1, RP11- 433A23.1 , SOCS6 , RTTN, ESCOl, SNRPD1, ABHD3, MBD2, POLI, STARD6, C18orf54, DYNAP, RAB27B, CD226, CCDC68, TCF4, RNF152, PIGN, KIAA1468, TNFRSF11A, ZCCHC2, PHLPP1, AC015989.1, AC015989.2, BCL2, MC4R, SERPINB5, SERPINB12 , SERPINB13 , SERPINB4,
SERPINB3, SERPINB7, SERPINB2, SERPINB10, AC009802.1, HMSD, SERPINB8, CDH20, VPS4B, DOK6, DSEL, KDSR, PMAIP1, NARS, ATP8B1, NEDD4L, ALPK2, MALT1, ZNF532, SEC11C, GRP, RAX, CPLX4, LMAN1, CCBE1, TMX3 , TXNL1, CDH19, FECH, CCDC102B, RP11-861L17.3 , WDR7 , CDH7 , BOD1L2, ST8SIA3 , ONECUT2, GALR1, CBLN2, RP11-723G8.2 , NETOl, RP11-169F17.1 , RP11- 321M21.3, C18orf62, RP11-94B19.4, ZNF516, RP11-17M16.1 , RP11- 111H3.1, RP11-162A12.2, ZNF236, MBP, ZADH2 , TSHZ1, ZNF407, FBX015, TIMM21, CYB5A, C18orf63, FAM69C, CNDP2 , CNDP1, and SALL3;
(iii) segment 3: SGCG, SACS, TNFRSF19 , MIPEP, AL139080.1, C1QTNF9B, SPATA13, C1QTNF9, C1QTNF9B-AS1 , PARP4, ATP12A, RNF17, CENPJ, LSP1, PABPC3, FAM123A, MTMR6, NUPL1, ATP8A2, AL138815.1, AL138815.2, SHISA2, RNF6, CDK8, WASF3, GPR12, USP12, RPL21, RASL11A, GTF3A, MTIF3, LATS2, SAP18, SKA3 , MRP63, ZDHHC20, ZDHHC20, EFHA1, FGF9, LNX2, POLR1D, GSX1, PDX1, RXFP2 , FRY, ZAR1L, BRCA2 , N4BP2L1, RP11-298P3.4, N4BP2L2, PDS5B, KL, STARD13, RFC3, SLC7A1, PA 3 , ATP5EP2, CDX2, PRHOXNB, FLT3, UBL3, LINC00544, KATNAL1, HMGB1,
USPL1, ALOX5AP, MEDAG, TEX26, HSPH1, B3GALTL, FLT1, POMP, SLC46A3,
MTUS2, NBEA, DCLK1, MAB21L1, CCNA1 , SOHLH2 , CCDC169-SOHLH2 , CCDC169, SPG20, SPG20OS, SERTM1, DLEU1 , RFXAP, FAM124A, SERPINE3, INTS6, WDFY2, DHRS12, CCDC70, ATP7B, ALG11, UTP14C, RNASEH2B, DLEU7 , LECT1, PCDH8, OLFM4, PRR20A, PRR20B, PRR20C, PRR20D, PRR20E, PCDH17, TDRD3, and DIAPH3;
(iv) segment 4: MRE11A, CTSC, FAT3 , MTNR1B, SLC36A4, CCDC67, Cllorf75, KIAA1731, TAF1D, Cllorf54, MED17, VSTM5, HEPHL1, DYNC2H1, RAB38, TMEM135, CEP57, USP35, GAB2 , MTMR2 , GUCY1A2, ANKRD49, PIWIL4, FUT4, AMOTL1, KDM4D, KDM4E, ENDOD1, SESN3, FAM76B, KCTD21, PANX1, DCUN1D5, NARS2, CNTN5 , AAMDC, INTS4, KCTD14, NDUFC2 -KCTD14 , THRSP, NDUFC2, ALG8, ARHGAP42 , TMEM133, PGR, TENM4, RP11 -817J15.3 , MMP27, RSF1, Cllorf53, Cllorf92, Cllorf93, POU2AF1, RP11-794P6.2 , BTG4, Cllorf88, LAYN, SIK2, PPP2R1B, MMP8, MMP10, MMP1, MMP3, MMP13, ALG9, CWF19L2, ALKBH8, AP000889.3, TMEM123, MMP20, PDGFD, DDI1, FZD4, TRPC6, ANGPTL5, KIAA1377, Cllorf70, YAP1, BIRC3, BIRC2, RP11- 31506.2, MMP7, ALG9, FDX1 , ARHGAP20 , PRSS23, MSANTD4, KBTBD3,
AASDHPPT, TMEM126B, TMEM126A, CREBZF, CCDC89, SYTL2, AP000974.1, CCDC83, PICALM, EED, Cllorf73, CCDC81, ME3 , DLG2 , ZC3H12C, RDX, GRIA4, FAM181B, PRCP, Cllorf82, RAB30, PCF11, ANKRD42, CCDC90B, ELMOD1, Cllorf87, CASP12, CASP4, CASP5, CASP1, CARD16, CARD17,
CARD18, Cllorfl, FDXACB1, Cllorf65, SLN, AP002353.1, AP001024.2, AP001024.1, SLC35F2, RAB39A, CRYAB, CUL5, ACAT1, NPAT, ATM,
AP001925.1, KDELC2, EXPH5, DDX10, FOLR4 , GPR83, HSPB2, DLAT, PIH1D2, Cllorf57, TIMM8B, SDHD, DIXDCl, HSPB2-Cllorf52 , Cllorf52, IL18, SDHD, TEX12, BC02 , and PTS;
(v) segment 5: SDAD1, AC110615.1, CXCL9, ART3, CXCL10, CXCL11, NUP54, SCARB2, FAM47E, STBD1, CCDC158, SHROOM3, SOWAHB, Sep-11, CCNI, CCNG2, CXCL13, CNOT6L, MRPL1, AFM, AFP, ANXA3, BMP2K, PAQR3, NAA11, GK2, ANTXR2, PRDM8 , FGF5, C4orf22, BMP3, PRKG2, RASGEF1B, HNRNPD, HNRPDL, ENOPH1, TMEM150C, SCD5, SEC31A, THAP9, LIN54, COPS4, PLAC8, COQ2, HPSE, HELQ, MRPS18C, FAMI 75A, AGPAT 9 , NKX6-1, CDS1, WDFY3, COX18, ANKRD17, ALB, NAAA, RASSF6, IL8, CXCL6, PF4V1, CXCL1, PF4, PPBP, CXCL5, CXCL3, CXCL2, AC093677.1, FRAS1, BTC, PARM1, RCHY1, THAP6, C4orf26, CDKL2, G3BP2, USOl, PPEF2, SLC4A4, GC,
NPFFR2, ADAMTS3, LPHN3, TECRL, UGT2B15, UGT2B10, UGT2A3, UGT2B7, UGT2B11, UGT2B28, UGT2B4, UGT2A1, SULT1B1, SULT1E1, CSN1S1, CSN2,
STATH, HTN3, HTN1 , C4orf40, ODAM, FDCSP, CSN3, CABS1, SMR3A, SMR3B, PROL1, MUC7, AMTN, AMBN, ENAM, IGJ, UTP3, RUFY3, GRSF1, MOBIB , DCK, ARHGAP24, MAPK10, AFF1, UGT2B17, EPHA5, TMPRSSllBNL, TMPRSS11B, YTHDC1, TMPRSS11E, KLHL8, C4orf36, HSD17B13, HSD17B11, SLC10A6, NUDT9, RP11-9B6.1, PTPN13, SPARCL1, DSPP, DMP1, IBSP, MEPE, SPP1, PKD2, ABCG2, PPM1K, HERC6, HERC5, PYURF, HERC3, PIGY, NAP1L5,
FAM13A, TIGD2, GPRIN3, SNCA, MMRN1, GRID2, ATOH1, SMARCAD1 , HPGDS, PDLIM5, TMPRSS11F, RP11-763F8.1 , FAM190A, BMPR1B, CPEB2, C1QTNF7, CC2D2A, FBXL5, FAM200B, BST1, CD38, FGFBP1, FGFBP2, PROM1 , TAPT1, LDB2, QDPR, CLRN2 , LAP3, MED28, FAM184B, DCAF16, NCAPG, LCORL, HAUS3, MXD4, ZFYVE28, RP11 -503N18.3 , RNF4, FAM193A, TNIP2, SH3BP2,
ADD1, MFSD10, NOP14, GRK4 , HTT, MSANTD1, RGS12, HGFAC, DOK7, LRPAP1, AL590235.1, RP3-368B9.1, ADRA2C, OTOP1, TMEM128, LYAR, ZBTB49 , NSG1, STX18, MSX1, CYTL1, STK32B, C4orf6, EVC2 , EVC, CRMP1, C4orf50, JAKMIP1, WFS1, PPP2R2C, MAN2B2, MRFAP1, AC093323.1, S100P, MRFAP1L1, BLOC1S4, KIAA0232, TBC1D14, CCDC96, TADA2B, GRPEL1, SORCS2, PSAPL1, AFAP1, AC097381.1, ABLIM2, SH3TC1, HTRA3, ACOX3, TRMT44, GPR78, CPZ, HMX1, RAB28, NKX3-2, BOD1L1, POLN, WDR1 , ZNF518B, CLNK, HS3ST1, SLIT2, PACRGL, KCNIP4, GPR125, GBA3, AC093917.1, PPARGC1A, DHX15, SOD3, CCDC149, LGI2, SEPSECS, PI4K2B, ZCCHC4, ANAPC4, SLC34A2, SEL1L3, C4orf52, RBPJ, CCKAR, TBC1D19, STIM2, RP11-180C1.1 , WHSC2, C4orf48, NAT8L, WHSC1, UNC5C, TLR3, FAM149A, AC110771.1, CYP4V2, KLKB1, Fll, MTNR1A, FAT1, SORBS2, WWC2 , CLDN22, CLDN24, CDKN2AIP, ING2, RWDD4, TRAPPC11, STOX2, ENPP6, IRF2, CASP3, CCDC111, MLF1IP, ACSL1, RP11-701P16.2, HELT, SLC25A4, KIAA1430, SNX25, LRP2BP,
ANKRD37, UFSP2, C4orf47, CCDC110, RP11 -27909.4 , PDLIM3 , PDHA2, TENM3, and DCTD;
(vi) segment 6: KCTD12, IRG1, CLN5, FBXL3, MYCBP2, SCEL,
SLAIN1, C13orf45, LM07, COMMD6, UCHL3, and TBC1D4;
(vii) segment 7: EDNRB, POU4F1, RNF219, SPRY2, RBM26, NDFIP2, SLITRK6, SLITRK5, IRS2, MY016, COL4A1, COL4A2, COL4A2-AS2, RAB20,
CARKD, NALCN, ITGBL1, CARS2 , ING1, TM9SF2, CLYBL, GPC5, ZIC5, ZIC2, UBAC2, GPR18, GPR183, DAOA, FGF14, TEX30, KDELC1, BIVM, ERCC5, SLC10A2, EFNB2, ARGLU1, IP05, FARP1, RNF113B, STK24, SLC15A1, DOCK9, TPP2, METTL21C, CCDC168, OXGR1 , MBNL2, RAP2A, LINC00346, and
ANKRD10;
(viii) segment 8: FTSJD1, AP1G1, ATXN1L, IST1, ZNF821, IST1,
DHODH, TXNL4B, HP, HPR, DHX38, PMFBP1, PHLPP2, MARVELD3 , CALB2, ZNF23, ZNF19, ZNF19, CHST4, and TAT;
(ix) segment 9: SORCS1, CYP2C18, CYP2C19, CYP2C9, CYP2C8, NRG3, SORCS3, C10orfl29, PDLIM1, SORBS1, HELLS, GRID1, ALDH18A1, RP11-476E15.3, FAM190B, HPSE2, GHITM, C10orf99, CDHR1, LRIT2, LRIT1, RGR, HTR7, RPP30, ANKRD1, TCTN3, ENTPD1, C10orfl31, CC2D2B, CCNJ, BLNK, DNTT, OPALIN, TLL2, TM9SF3, PIK3AP1, LCOR, C10orfl2, SLIT1, ARHGAP19 , FRAT1, FRAT2, RRP12, AL355490.1, PGAM1 , EXOSC1, ZDHHC16 , MMS19, UBTD1, ANKRD2, HOGA1 , PI4K2A, PI4K2A, C10orf62, MOR 4 , AVPI1, MARVELD1, ZFYVE27, SFRP5, GOLGA7B, CRTAC1, AL358938.1, R3HCC1L,
LOXL4, PYROXD2, HPS1, PCGF5, CNNM1, GOT1, NKX2-3, SLC25A28, ENTPD7, CUTC, COX15, ABCC2, DNMBP, CPN1 , ERLIN1, CHUK, PANK1 , CWF19L1, BLOC1S2, PKD2L1, SCD, WNT8B, SEC31B, NDUFB8, NDUFB8, HIF1AN, PAX2, FAM178A, SLC16A12, KIF20B, WAPAL, OPN4 , IFIT1B, IFIT1, IFIT5,
TBC1D12, PPP1R3C, TNKS2, FGFBP3, BTAF1 , HECTD2, CPEB3, CCDC147,
SEMA4G, NOC3L, LIPA, MRPL43, Mar-05, MINPP1, PAPSS2, ATAD1, KLLN, PTEN, INPP5F, ANKRD22, STAMBPL1, ACTA2 , FAS, CH25H, IFIT2, IFIT3, IDE, TRUB1, MCMBP, SEC23IP, DPCD, POLL, FBXW4, FGF8, NPM3 , MGEA5, KCNIP2, FAM160B1, BTRC, ABLIM1, ATRNL1, RGS10, TIAL1, BAG3,
C10orf76, PPAPDC1A, C10orf85, KIF11, HHEX, EXOC6, CYP26C1, CYP26A1, MYOF, CEP55, 03FAR1, RBP4, PDE6C, FRA10AC1, LGI1, SLC35G1, PCGF6, TAF5, USMG5, XPNPEP1, GRK5, GPAM, TECTB, ACSL5, ZDHHC6, VTI1A, TCF7L2, HABP2, NRAP, CASP7, PLEKHS1, DCLRE1A, NHLRC2, AL162407.1, ADRB1, C10orfll8, TDRD1, VWA2 , AFAP1L2, C10orf2, LZTS2, PDZD7, SFXN3, KAZALD1, HUG1, TLX1, LBX1 , RNLS, LIPJ, LIPF, LIPK, LIPN,
LIPM, PLCE1, HPS6, LDB1, PPRC1, NOLC1, ELOVL3, PITX3, GBF1, NFKB2, PSD, FBXL15, CUEDC2, C10orf95, TMEM180, ACTR1A, SUFU, TRIM8, ARL3, SFXN2, WBP1L, CYP17A1, C10orf32, AS3MT, CNNM2 , NT5C2, INA, PDCD11, VAX1, KCNK18, SLC18A2, PDZD8, RP11 -451M19.3 , ADD3, MXI1, SMNDC1, DUSP5, SMC3, RBM20, PDCD4, BBIP1, SHOC2, ADRA2A, TEX36, CALHM2, CALHM1, CALHM3, NEURL, FANK1 , DHX32, SFR1, WDR96, GSTOl, GST02, ITPRIP, CTBP2, EMX2 , RAB11FIP2, FAM204A, SH3PXD2A, C10orfl37,
AL158835.1, MMP21, UROS, BCCIP, KIAA1598, OBFC1, COL17A1, SLK, CACUL1, NANOS1, EIF3A, FAM45A, SFXN4, PRDX3, OAT, NKX1-2, LHPP, RP11-12J10.3, FAM53B, METTL10, FAM175B, ZRANB1, WDR11, GPR26, CPXM2, EN04, PRLHR, CHST15, FGFR2, ATE1, NSMCE4A, TACC2 , CCDC172, PNLIPRP3,
PNLIP, PNLIPRP1, C10orf82, HSPA12A, BTBD16 , PLEKHA1, ARMS2 , HTRA1,
DMBT1, C10orfl20, CUZD1, FAM24B, FAM24A, C10orf88, GFRA1 , PSTK, NPS, IKZF5, ACADSB, HMX3 , HMX2 , BUB3, FOXI2, MGMT, AL355531.2, EBF3, GLRX3, MKI67, and PTPRE;
(x) segment 10: NTN5, FUT2, MAMSTR, RASIP1, IZUMOl, FUT1, FGF21, BCAT2, HSD17B14, PLEKHA4, PPP1R15A, TULP2, NUCB1, DHDH, BAX, FTL, GYS1, RUVBL2, LHB, CGB, CTB-60B18.6, CGB2 , CGB1, CGB5, CGB8, CGB7, NTF4, KCNA7 , SNRNP70, LIN7B, C19orf73, PPFIA3, HRC, TRPM4, SLC6A16, CCDC114, EMP3, TMEM143, SYNGR4, KDELR1, GRIN2D, GRWD1, KCNJ14, CTC-273B12.7, CYTH2, LMTK3, SULT2B1, FAM83E, SPACA4, RPL18, SPHK2, DBP, CA11, AC011450.1, CD37, TEAD2, DKKL1, CCDC155, PTH2, CTD-3148I10.1, SLC17A7 , PIH1D1, ALDH16A1, CTD-3148I10.9, FLT3LG, RPL13A, RPS11, hsa-mir-150, FCGRT, RCN3, NOSIP, PRRG2 , PRR12, RRAS, SCAF1, IRF3, BCL2L12, PRMT1, ADM5, CPT1C, TSKS, AP2A1, FUZ, MED25, PTOV1, PNKP, AKT1S1, TBC1D17, IL4I1, NUP62, SIGLECll, ATF5,
SIGLECll, VRK3, ZNF473, IZUM02, MYH14, KCNC3, NR1H2, NAPSA, POLD1, SPIB, SPIB, KPTN, NAPA, ZNF541, GLTSCR1, EHD2, GLTSCR2, SEPW1, TPRX1, MYBPC2, SLC8A2, FAM71E1, LRRC4B, EMC10, JOSD2, ASPDH, BBC3, CCDC9, PRR24, C5AR1, GPR77, DHX34, MEI S3 , NLRP13, SYT3, C19orf81, NLRP8, NLRP5, ZNF787, ZNF444, AC024580.1, GALP, ZSCAN5B, ZSCAN5C, ZSCAN5A, ZSCAN5D, AC006116.20, ZNF582, ZNF583, ZNF667, ZNF471,
ZFP28, ZNF470, SHANK1 , CLEC11A, GPR32, ACPT, C19orf48, KLK1, KLK15, KLK3, KLK2, AC037199.1, KLK4 , KLK5 , KLK6, KLK7 , KLK8 , KLK9, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14, CTU1 , SIGLEC9, SIGLEC7, CD33, SIGLECLl, IGLON5, VSIG10L, ETFB, CTD-2616Jll.il, CLDND2, NKG7, LIM2, CTD-2616J11.4, SIGLEC10, SIGLEC8, CEACAM18 , SIGLEC12, SIGLEC6, ZNF175, AC018755.il, HSPBP1, BRSK1 , PPP6R1, TMEM150B, SUV420H2, SUV420H2, COX6B2, CTD-2105E13.6, FAM71E2, IL11, TMEM190, TMEM238, RPL28, UBE2S, SHISA7, ISOC2, ZNF628, NAT14, SSC5D, SBK2, SGK110, ZNF579, FIZ1, ZNF524, ZNF865, ZNF784, ZNF580, ZNF581, CCDC106, U2AF2, EPN1, NLRP9, RFPL4A, PTPRH, TMEM86B, AC010327.2, SYT5, CTD- 2611012.2, NLRP11, NLRP4, SIGLEC5, SIGLEC5, TNNT1, TNNI3, CTD- 2587H24.4, DNAAF3, PPP1R12C, MYADM, PRKCG, CACNG7, CACNG8, CACNG6, VSTM1, TARM1, OSCAR, NDUFA3, TFPT, PRPF31, CNOT3, LENG1 , TMC4, MBOAT7, TSEN34, RPS9, LILRB3, LILRA6, LILRB5, LILRB2, LILRA3,
LILRA5, LILRA4, LAIR1, TTYH1, LENG8 , LENG9, CDC42EP5, LAIR2,
KIR3DX1, LILRA2, LILRB1, LILRA1, AC009892.10, LILRB4, KIR3DL1,
KIR3DL3, KIR2DL4, KIR2DL3, KIR2DL1, KIR3DL2, FCAR, NCR1 , NLRP7, NLRP2, GP6, CTC-550B14.6, RDH13, EPS8L1, ZNF677, VN1R2, VN1R4, BIRC8, ZNF845, ZNF525, ZNF765, ZNF813, ZNF331, CTB-167G5.5, DPRX, NLRP12, ZNF615, ZNF701, SIGLEC14, HAS1, ZNF614, ZNF432, ZNF841, ZNF616, ZNF836, PPP2R1A, ZNF766, ZNF480, ZNF610, ZNF880, ZNF528, ZNF534, ZNF578, ZNF808, ERW-1, ERVV-2, ZNF160, ZNF415, ZNF347,
ZNF665, FPR2, ZNF321P, ZNF816, ZNF83, FPR1, ZNF611, ZNF600, ZNF28, ZNF468, ZNF320, ZNF577, ZNF649, ZNF613, ZNF350, and FPR3;
(xi) segment 11: NUP155, GOLPH3, WDR70, PDZD2, C5orf22,
PTGER4, TTC33, PRKAA1 , RPL37, CARD6, C7, HEATR7B2, C6, PLCXD3, MTMR12, OXCT1, C5orf51, FBX04, CCDC152, SEPP1, GHR, GDNF, EGFLAM, LIFR, AC091435.1, AC091435.2, OSMR, RICTOR, FYB, AC008964.1, C9, DAB2 , DROSHA, Mar-11, C5orf42, ANXA2R, ZNF131, ZFR, NIPBL, FBXL7, SLC1A3, CDH9, MRPS30, FAM134B, SPEF2, IL7R, CAPSL, UGT3A1, UGT3A2, LMBRD2, SKP2, NADKD1, RANBP3L, SUB1, NPR3 , AC026703.1, NNT, FGF10, TARS, ZNF622, NIM1, ADAMTS12 , RXFP3, SLC45A2, AMACR, C1QTNF3, RAI14, TTC23L, RAD1, BRIX1, DNAJC21, AGXT2, HMGCS1, CCL28, C5orf28,
C5orf34, PAIP1, PRLR, AC010368.2, PRDM9, MYO10, CDH10, C5orfl7, and CDH6;
(xii) segment 12: CNTLN and CCDC171;
(xiii) segment 13: SNURF, AVEN, CHRM5, EMC7 , PGBD4, KATNBL1,
EMC4 , GJD2, ACTC1, AQR, ZNF770, AC114546.1, GABRB3, GABRA5, GABRG3, UBE3A, ATP10A, ATPBD4, TMC05A, RYR3, SPRED1, FAM98B, RASGRP1,
C15orf53, C15orf54, THBS1, FSIP1, C15orf41, C15orf23, IVD, SQRDL, CHST14, CASC4, CTDSPL2, EIF3J, RP11-82I10.1, PHGR1, DISP2, MEIS2 , MEX3B, RP11-597K23.2, SQRDL, TMC3, SPG11, SPATA5L1, C15orf48,
SLC30A4, BLOC1S6, STARD5, BAHD1, GATM, TRIM69, C15orf43, HOMER2 , FAM103A1, C15orf40, BTBD1, TM6SF1, HDGFRP3, BNC1, TMED3, KIAA1024, MTHFS, ST20-MTHFS, ST20, C15orf37, C150RF37, BCL2A1, ZFAND6, FAH, KLHL25, LRRC57, HAUS2, STARD9, CDAN1, TTBK2 , AC015660.1, LYSMD4, DKFZP779J2370, CTD-2054N24.2 , ADAMTS17, C15orf57, MEF2A, SLC28A2, WHAMM, SORD, DUOX2, DUOXA2 , DUOXA1, DUOX1 , SHF, SNAP23, AGBL1, C15orf52, ARRDC4, AP3B2, FSD2, CHRNA3 , CHRNB4, ADAMTS7, MORF4L1, CTSH, RASGRF1, ANKRD34C, ZFP106, CHRNA5, PLCB2 , IREB2, AGPHD1, AC027228.1, PSMA4, TTLL13, RP11-697E2.6, NGRN, GABARAPL3, ZNF774, IQGAP1, CRTC3, BLM, FURIN, FES, MAN2A2, UNC45A, HDDC3, RCCD1, PRC1, VPS33B, C15orf56, RP11-133K1.2 , PAK6, IL16, ANKRD63, GPR176,
EIF2AK4, SRP14, RP11-210M15.2 , ARNT2, FAM108C1, KIAA1199, RP11- 351M8.1, MESDC2, MESDC1, C15orf26, PATL2, B2M, SV2B, PPP1R14 D, SPINT1, RHOV, VPS18, DLL4, CHAC1, LRRC28, AC022819.4, RPUSD2, BMF, BUB1B , ZFYVE19 , MCTP2, AC016251.1, NR2F2, AC087477.1, SPATA8 ,
GDPGP1, CHD2, RGMA, AC112693.2, ZNF710, IDH2, SEMA4B, CIB1, FKSG62, FAM82A2, TTC23, DNAJC17, FAM174B, CASC5, SYNM, GCHFR, C15orf62,
INO80, EXD1, CHP1, OIP5, NUSAP1, NDUFAF1, RTF1, ITPKA, LTK, RPAP1, CAPN3, PGPEP1L, WDR61, and CRABP1;
(xiv) segment 14: C21orf37, C21orf91, CXADR, BTG3, USP25, CHODL, KRTAP21-3, KRTAP21-2 , KRTAP21-1, KRTAP8-1, KRTAPll-1,
KRTAP19- 6 , KRTAP19-7 , KRTAP22-2, KRTAP6-3, KRTAP6-2, KRTAP22-1, KRTAP6-1, KRTAP20-1, KRTAP20-4, KRTAP20-2 , KRTAP20-3 , KRTAP19-1 , KRTAP19-2 , KRTAP19-3 , KRTAP19-4 , KRTAP19-5 , CBR1, CBR3, DOPEY2, MORC3, SETD4, SOD1, SCAF4, CHAF1B, CLIC6, AP000695.1, HUNK, MIS18A, MRAP, URB1, C21orfll9, AP000688.1, CLDN14, KCNE2, FAM165B,
AP000322.54, AP000322.53, EVA1C, KRTAP19-8 , TCP10L, C210RF59,
C21orf59, and SYNJ1;
(xv) segment 15: XKR9, RP11-758M4.1, PI15, CRISPLD1, HNF4G, PEX2, and GDAP1; and
(xvi) segment 16: ZNF724P, ZNF91, ZNF66P, ZNF626, ZNF730, ZNF98, ZNF492, and ZNF99.
13. The method according to claim 12, wherein determining the CNA status of each genomic segment comprises determining the copy number of all of said loci within each genomic segment.
14. The method according to any one of the preceding claims, wherein copy number aberration CNA status is determined for not more than 20 genomic segments, totalling not more than 600 megabase pairs (Mbp) in length.
15. The method according to any one of the preceding claims, wherein the sample is classified as being chemosensitive, said method further comprising the step of selecting or recommending the subject for a course of chemotherapy for SCLC.
16. The method according to claim 15, wherein said chemotherapy comprises a platinum-based chemotherapeutic, optionally cisplatin, carboplatin or oxaplatin.
17. The method according to claim 15 or claim 16, wherein said chemotherapy comprises etoposide.
18. The method according to any one of claims 1 to 14, wherein the sample is classified as being chemorefractory, said method further comprising the step of selecting or recommending the subject for treatment other than chemotherapy with a platinum-based
chemotherapeutic and/or etoposide.
19. The method according to claim 18, wherein said treatment other than chemotherapy with a platinum-based chemotherapeutic and/or etoposide comprises alternative or experimental therapy, optionally enrolment in a clinical trial for an experimental SCLC treatment.
20. The method according to any one of the preceding claims, wherein the method further comprises the step of providing a prognosis of the likely course of the subject's SCLC based on the classification of the sample as being chemosensitive or
chemorefractory .
21. The method according to claim 20, wherein the prognosis comprises an estimate of progression-free survival (PFS) time and/or overall survival (OS) time.
22. The method according to any one of the preceding claims, wherein determining the CNA status of said at least 10 genomic segments of said CTC sample comprises a step of next-generation sequencing (NGS) of DNA obtained from said CTC sample or amplified from said CTC sample.
23. The method according to any one of the preceding claims, wherein DNA obtained from said CTC sample is amplified by whole genome PCR.
24. The method according to any one of the preceding claims, wherein said CTC sample is obtained from a blood sample taken from said subject, and wherein the said blood sample is processed to enrich and/or isolate CTCs.
25. The method according to claim 24, wherein processing said blood sample to enrich and/or isolate CTCs employs markers selected from the group consisting of:
CD45-;
EpCAM+; and
cytokeratins 8, 18+, and/or 19+.
26. The method according to any one of the preceding claims, wherein determining the CNA status of said at least 10 genomic segments of said CTC sample comprises comparing CTC copy number with a germline control obtained from the same subject.
27. The method according to claim 26, wherein said germline control comprises DNA obtained from a white blood cell (WBC) sample or amplified from said WBC sample.
28. The method according to any one of the preceding claims, wherein the subject has been diagnosed as having SCLC.
29. The method according to any one of the preceding claims, wherein the subject has not completed a course of chemotherapy for SCLC.
30. The method according to claim 29, wherein the subject has not started a course of chemotherapy for SCLC.
31. A method for stratifying a population of subjects according to SCLC chemosensitivity, the method comprising carrying out the method of any one of claims 1 to 30 on each of the subjects in the
population .
32. A system for carrying out the method of any one of claims 1 to 31, the system comprising:
a computer-readable storage medium which stores computer- executable instructions for applying a computational classifier to a dataset comprising one or more sample CNA profiles, said
computational classifier comprising a machine learning model trained on a set of training CNA profiles of at least 10 genomic segments obtained from training samples of known
chemosensitive/chemorefractory status, which training samples include at least two known chemosensitive SCLC CTC samples and at least two known chemorefractory SCLC CTC samples; and
a processor which is configured to perform steps comprising receiving said dataset and executing said computer-executable instructions stored in said computer-readable storage medium, wherein said at least 10 genomic segments are selected from the group of genomic segments consisting of:
Segment- 1 : chromosome 16, start : 53467889, end : 87739290;
Segment- 2 : chromosome 18, start : 2537524, end: 76762677
Segment- 3: chromosome 13, start : 21547171, end: 61148012
Segment- 4 : chromosome 11, start : 77371041, end : 112140678
Segment- 5: chromosome 4, start: 1873151, end: 187647876
Segment- 6: chromosome 13, start : 75858808, end: 78338377
Segment- 7 : chromosome 13, start : 78469616, end : 111567416
Segment- 8 : chromosome 16, start : 71315292, end: 72210777
Segment- 9: chromosome 10, start : 83635070, end : 131982785
Segment- 10 chromosome 19, start : 47724081, end : 57100279
Segment- 11 chromosome 5, start : 15500305, end: 44820530
Segment- 12 chromosome 9, start : 15552895, end: 17503921
Segment- 13 chromosome 15, start : 25200133, end : 100882210
Segment- 14 chromosome 21, start : 17102344, end : 37860058
Segment- 15 chromosome 8, start : 71581600, end: 77913280
Segment- 16 chromosome 19, start : 20802867, end : 23578362,
wherein said start and end positions are according to the numbering system of Genome Reference Consortium GRCh37 patch release 13, dated 28 June 2013.
33. The system according to claim 32, wherein the computational classifier comprise a SVM or a PLS regression.
34. The system according to claim 33, wherein the SVM comprises a Gaussian Radial Basis kernel function, and wherein the parameters that support the classifier are as follows:
parameter : cost C = 0.25
Hyperparameter : sigma = 0.0476184222095904
Number of Support Vectors : 43.
35. The system according to any one of claims 32 to 34, further comprising an output module configured to output the
chemosensitive/chemorefractory classification of the or each CNA profile in the dataset.
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