KR970706849A - 신규의 종양 억제 유전자 에이치아이씨(hic)-1(novel tumor suppressor gene. hic-1) - Google Patents
신규의 종양 억제 유전자 에이치아이씨(hic)-1(novel tumor suppressor gene. hic-1) Download PDFInfo
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- 102000044209 Tumor Suppressor Genes Human genes 0.000 title claims 3
- 108700025716 Tumor Suppressor Genes Proteins 0.000 title claims 3
- 102100031612 Hypermethylated in cancer 1 protein Human genes 0.000 title abstract 5
- 101710133850 Hypermethylated in cancer 1 protein Proteins 0.000 title abstract 5
- 238000000034 method Methods 0.000 claims abstract 36
- 108091033319 polynucleotide Proteins 0.000 claims abstract 14
- 102000040430 polynucleotide Human genes 0.000 claims abstract 14
- 239000002157 polynucleotide Substances 0.000 claims abstract 14
- 201000010099 disease Diseases 0.000 claims abstract 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 12
- 229920001184 polypeptide Polymers 0.000 claims abstract 7
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract 7
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 7
- 230000002062 proliferating effect Effects 0.000 claims abstract 7
- 150000007523 nucleic acids Chemical group 0.000 claims 12
- 210000004027 cell Anatomy 0.000 claims 10
- 102000039446 nucleic acids Human genes 0.000 claims 10
- 108020004707 nucleic acids Proteins 0.000 claims 10
- 239000000523 sample Substances 0.000 claims 9
- 210000003850 cellular structure Anatomy 0.000 claims 6
- 239000003153 chemical reaction reagent Substances 0.000 claims 6
- 239000013604 expression vector Substances 0.000 claims 6
- 206010003571 Astrocytoma Diseases 0.000 claims 4
- 230000002518 glial effect Effects 0.000 claims 4
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 150000001875 compounds Chemical class 0.000 claims 3
- 230000011987 methylation Effects 0.000 claims 3
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- 239000002773 nucleotide Substances 0.000 claims 3
- 125000003729 nucleotide group Chemical group 0.000 claims 3
- 108091008146 restriction endonucleases Proteins 0.000 claims 3
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- 206010009944 Colon cancer Diseases 0.000 claims 2
- 108020004414 DNA Proteins 0.000 claims 2
- 206010014733 Endometrial cancer Diseases 0.000 claims 2
- 206010014759 Endometrial neoplasm Diseases 0.000 claims 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 2
- 206010029260 Neuroblastoma Diseases 0.000 claims 2
- 206010060862 Prostate cancer Diseases 0.000 claims 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 2
- 206010038389 Renal cancer Diseases 0.000 claims 2
- 210000004556 brain Anatomy 0.000 claims 2
- 210000001072 colon Anatomy 0.000 claims 2
- 208000029742 colonic neoplasm Diseases 0.000 claims 2
- 230000003412 degenerative effect Effects 0.000 claims 2
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- 210000003734 kidney Anatomy 0.000 claims 2
- 201000010982 kidney cancer Diseases 0.000 claims 2
- 208000032839 leukemia Diseases 0.000 claims 2
- 210000004072 lung Anatomy 0.000 claims 2
- 201000005202 lung cancer Diseases 0.000 claims 2
- 208000020816 lung neoplasm Diseases 0.000 claims 2
- 210000001672 ovary Anatomy 0.000 claims 2
- 108090000623 proteins and genes Proteins 0.000 claims 2
- 210000001550 testis Anatomy 0.000 claims 2
- 210000001541 thymus gland Anatomy 0.000 claims 2
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- 108091029523 CpG island Proteins 0.000 claims 1
- 238000009007 Diagnostic Kit Methods 0.000 claims 1
- 108090000790 Enzymes Proteins 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 claims 1
- 208000032612 Glial tumor Diseases 0.000 claims 1
- 206010018338 Glioma Diseases 0.000 claims 1
- 208000000172 Medulloblastoma Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 230000002159 abnormal effect Effects 0.000 claims 1
- 201000000053 blastoma Diseases 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 210000000038 chest Anatomy 0.000 claims 1
- 230000000295 complement effect Effects 0.000 claims 1
- 201000008184 embryoma Diseases 0.000 claims 1
- 238000001415 gene therapy Methods 0.000 claims 1
- 208000005017 glioblastoma Diseases 0.000 claims 1
- 238000009396 hybridization Methods 0.000 claims 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims 1
- 230000006607 hypermethylation Effects 0.000 claims 1
- 239000002184 metal Substances 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 238000003259 recombinant expression Methods 0.000 claims 1
- 238000012360 testing method Methods 0.000 claims 1
- 210000001519 tissue Anatomy 0.000 claims 1
- 241001430294 unidentified retrovirus Species 0.000 claims 1
- 210000002229 urogenital system Anatomy 0.000 claims 1
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 abstract 1
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 abstract 1
- 239000003550 marker Substances 0.000 abstract 1
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Abstract
본발명은 신규의 종양 억제인자 HIC-1을 암호화하는 폴리뉴클레오티드 및 폴리펩티드 서열을 제공한다. 본 발명은 또한 HIC-1과 관련된 세포 증식성 질환의 검출 방법을 제공한다. HIC-1은 그러한 질환의 경과중에, 진단적, 예후적 및 치료적으로 사용될 수 있는 마커이다.
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
Claims (48)
- 주로 서열번호 3의 아미노산 서열로 구성되는 실질적으로 순수한 HIC-1(암에서 과메틸화된) 폴리펩티드.
- 서열번호 3의 아미노산 서열을 가진 폴리펩티드를 암호화하는 폴리뉴클레오티드 서열로 주로 구성되는 분리된 폴리뉴클레오티드 서열.
- 제2항에 있어서, 서열번호 3의 아미노산 서열을 가진 폴리펩티드를 암호화하는 폴리뉴클레오티드 서열로 주로 구성되고, HIC-1 폴리펩티드와 면역반응성이 있는 항체에 대한 하나 이상의 에피토프를 가지는 분리된 폴리뉴클레오티드 서열.
- 제2항에 있어서, 뉴클레오티드 서열이 a) T가 U일수도 있는 서열번호 1의 서열; b) 서열 a)와 상보적인 핵산 서열; c) 15개 이상의 염기 길이를 가지고, HIC-1을 암호화하는 게놈 DNA에 선택적으로 혼성화하는 상기 a) 또는 b) 서열의 단편으로 구성된 군에서 선택되는 폴리뉴클레오티드.
- 제2항의 폴리뉴클레오티드를 포함하는 재조합 발현 벡터.
- 제5항의 발현 벡터를 포함하는 숙주 세포.
- 서열번호 3의 폴리펩티드에 결합하며, 서열번호 3의 면역반응성 단편과 결합하는 항체.
- 제7항에 있어서, 상기 항체가 다클론인 항체.
- 제7항에 있어서, 상기 항체가 단일클론인 항체.
- HIC-1을 포함하는 표적 세포 성분을 HIC-1과 반응하는 시약과 접촉시키는 단계 및 HIC-1을 검출하는 단계를 포함하는, 피험자에서 HIC-1과 관련된 세포 증식성 질환을 검출하는 방법.
- 제10항에 있어서, 상기 표적 세포 성분이 핵산인 방법.
- 제11항에 있어서, 핵산이 DNA인 방법.
- 제11항에 있어서, 핵산이 RNA인 방법.
- 제11항에 있어서, 핵산이 과메틸화된 것인 방법.
- 제10항에 있어서, 상기 표적 세포 성분이 단백질인 방법.
- 제10항에 있어서, 상기 시약이 프로브인 방법.
- 제16항에 있어서, 상기 프로브가 핵산인 방법.
- 제16항에 있어서, 상기 프로브가 항체인 방법.
- 제18항에 있어서, 상기 항체가 다클론인 항체.
- 제18항에 있어서, 상기 항체가 단일클론인 항체.
- 제16항에 있어서, 상기 프로브가 검출가능하게 표지된 것인 방법.
- 제21항에 있어서, 상기 표지가 방사성 동위원소, 생물발광성 화합물, 화학 발광성 화합물, 형광성 화합물, 금속 킬레이트 또는 효소로 구성된 군에서 선택되는 방법.
- 제10항에 있어서, 상기 시약이 제한 엔도뉴클레아제인 방법.
- 제23항에 있어서, 상기 제한 엔도뉴클레아제가 메틸화에 민감성인 방법.
- 제24항에 있어서, 상기 제한 엔도뉴클레아제가 Msp I, Hpa Ⅱ, BssH Ⅱ 및 Not I으로 구성된 군에서 선택되는 방법.
- 제10항에 있어서, 상기 세포 증식성 질환이 뇌, 결장, 비뇨생식기, 폐, 신장, 조혈, 가슴, 흉선, 고환, 난소 및 자궁으로 구성된 군에서 선택되는 조직과 관련된 방법.
- 제26항에 있어서, 상기 질환이 저급 신경교 성상세포종, 퇴화성 신경교 성상세포종, 신경교아세포종, 수아세포종, 결장암, 폐암, 신장암, 백혈병, 유방암, 전립선암, 자궁내막암 및 신경아세포종으로 구성된 군에서 선택되는 방법.
- HIC-1과 과련된 세포 증식성 질환을 가진 환자에게 HIC-1의 발현을 조절하는 시약을 치료학적으로 유효한 양으로 투여하는 단계를 포함하는, HIC-1과 관련된 세포 증식성 질환의 치료 방법.
- 제28항에 있어서, 상기 시약이 HIC-1 센스 폴리뉴클레오티드 서열을 포함하는 폴리뉴클레오티드 서열인 방법.
- 제29항에 있어서, 추가로 포함되는 시약이 HIC-1 폴리뉴클레오티드 서열과 작동적 연결 관계인 프로모터를 암호화하는 폴리뉴클레오티드 서열인 방법.
- 제29항에 있어서, 상기 폴리뉴클레오티드 서열이 발현 벡터내에 존재하는 방법.
- 제28항에 있어서, 상기 질환이 뇌, 비뇨생식기, 폐, 결장, 신장, 조혈, 가슴, 흉선, 고환, 난소 및 자궁으로 구성된 군에서 선택되는 조지과 관련된 방법.
- 제32항에 있어서, 상기 질환이 저급 신경교 성상세포종, 퇴화성 신경교 성상세포종, 신경교아세포종, 수아세포종, 결장암, 폐암, 신장암, 백혈병, 유방암, 전립선암, 자궁내막암 및 신경아세포종으로 구성된 군에서 선택되는 방법.
- 제28항에 있어서, HIC-1 관련 세포 증식성 질환이 HIC-1 뉴클레오티드 서열의 과메틸화와 관련된 방법.
- HIC-1을 암호화하고 프로모터와 작동적 연결 관계에 있는 뉴클레오티드 서열을 포함하는 발현 벡터를 숙주 환자의 세포 속으로 도입시키는 것을 포함하는 유전자 치료 방법.
- 제35항에 있어서, 상기 발현 벡터를 환자의 세포내로 생체외에서 도입시키고, 그 세포를 다시 환자에게 도입시키는 방법.
- 제35항에 있어서, 상기 발현 벡터가 RNA 비루스인 방법.
- 제37항에 있어서, RNA 비루스가 레트로비루스인 방법.
- 제35항에 있어서, 상기 환자가 인간인 방법.
- 제35항에 있어서, 상기 질환이 HIC-1 폴리뉴클레오더드의 과메털화와 관련된 방법.
- 메틸화된 HIC-1 핵산의 검출용 프로브를 함유하는 제1용기를 포함하여 하나 이상의 용기를 내부에 밀착수용하도록 구획된 캐리어 수단을 포함하는, HIC-1 핵산의 메틸화와 관련된 세포 증식성 질환의 표시인 표적세포 성분의 검출에 유용한 진단 키트.
- 제41항에 있어서, 상기 표적 세포 성분이 HIC-1 폴리펩티드인 키트.
- 제42항에 있어서, 상기 프로브가 항체인 키트.
- 제41항에 있어서, 상기 표적 세포 성분이 핵산 서열인 키트.
- 제44항에 있어서, 상기 프로브가 폴리뉴클레오티드 혼성화 프로브인 키트.
- 핵산 샘플에서 비정상적인 핵산 메틸화를 검출하는 단계 및 유전자를 동정하는 단계를 포함하는 종양억제 유전자를 동정하는 방법.
- 제46항에 있어서, 상기 핵산이 하나 이상의 CpG 섬 뉴클레오티드 서열을 포함하는 방법.
- 제47항에 있어서, 상기 CpG 뉴클레오티드 서열이 과메틸화된 것인 방법.※ 참고사항 : 최초출원 내용에 의하여 공개되는 것임.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/340,203 US5756668A (en) | 1994-11-15 | 1994-11-15 | Hypermethylated in cancer polypeptide, HIC-1 |
US08/340,203 | 1994-11-15 |
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KR1019970703250A KR970706849A (ko) | 1994-11-15 | 1995-11-15 | 신규의 종양 억제 유전자 에이치아이씨(hic)-1(novel tumor suppressor gene. hic-1) |
Country Status (12)
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US (4) | US5756668A (ko) |
EP (1) | EP0792168A4 (ko) |
JP (1) | JPH10510145A (ko) |
KR (1) | KR970706849A (ko) |
CN (1) | CN1171743A (ko) |
AU (1) | AU4407196A (ko) |
BR (1) | BR9509674A (ko) |
CA (1) | CA2205414A1 (ko) |
FI (1) | FI972066A (ko) |
NO (1) | NO972228L (ko) |
NZ (1) | NZ298554A (ko) |
WO (1) | WO1996014877A1 (ko) |
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US6617434B1 (en) * | 1996-05-31 | 2003-09-09 | North Shore Long Island Jewish Research Institute | Identificiaton of differentially methylated and mutated nucleic acids |
US5871917A (en) | 1996-05-31 | 1999-02-16 | North Shore University Hospital Research Corp. | Identification of differentially methylated and mutated nucleic acids |
US6287854B1 (en) | 1996-10-22 | 2001-09-11 | Imperial Cancer Research Technology Limited | Diagnosis of susceptibility to cancer and treatment thereof |
US20050202499A1 (en) | 1996-10-31 | 2005-09-15 | Billing-Medel Patricia A. | Reagents and methods useful for detecting diseases of the breast |
EP0939824B1 (en) * | 1996-10-31 | 2007-06-06 | Abbott Laboratories | Reagents and methods useful for detecting diseases of the breast |
GB9710995D0 (en) * | 1997-05-28 | 1997-07-23 | Marie Curie Research Inst | Tumour suppressor locus and gene at 9q32-33 |
AU7829398A (en) | 1997-06-09 | 1998-12-30 | University Of Southern California | A cancer diagnostic method based upon dna methylation differences |
WO1999002714A1 (en) * | 1997-07-07 | 1999-01-21 | Abbott Laboratories | Reagents and methods useful for detecting diseases of the breast |
US20020037503A1 (en) * | 1997-11-17 | 2002-03-28 | Patricia A. Billing-Medel | Reagents and methods useful for detecting diseases of the breast |
SE513149C2 (sv) * | 1997-12-05 | 2000-07-17 | Katarina Edwards | Läkemedelsdistributionssystem med tvåstegsmålsökning, till specifika celler eller vävnad och till dess cellkärna |
US6994991B1 (en) | 1998-11-18 | 2006-02-07 | North Shore - Long Island Jewish Research Institute | Identification of differentially methylated multiple drug resistance loci |
US6783933B1 (en) * | 1999-09-15 | 2004-08-31 | The Johns Hopkins University School Of Medicine | CACNA1G polynucleotide, polypeptide and methods of use therefor |
US6911306B1 (en) * | 1999-10-18 | 2005-06-28 | Emory University | TMS1 compositions and methods of use |
US6468789B1 (en) | 2000-02-02 | 2002-10-22 | University Of Pittsburgh | Oxygen sensing and hypoxic selection for tumors |
WO2002002806A2 (en) * | 2000-06-30 | 2002-01-10 | Epigenomics Ag | Method and nucleic acids for analysing the methylation of genes implicated in pharmacogenomics |
WO2002068673A2 (en) * | 2001-02-23 | 2002-09-06 | Dana-Farber Cancer Institute, Inc. | Hin-1, a tumor suppressor gene |
JP2004524030A (ja) * | 2001-02-23 | 2004-08-12 | ザ ジョンズ ホプキンス ユニバーシティー スクール オブ メディシン | 膵臓がんにおけるメチル化の異なる配列 |
EP1432450B1 (en) * | 2001-10-03 | 2005-12-28 | Bioniche Life Sciences Inc. | Therapeutically useful triethyleneglycol cholesteryl oligonucleotides |
JP2007119359A (ja) * | 2005-10-25 | 2007-05-17 | Fujifilm Corp | 癌抑制剤 |
WO2009079208A2 (en) * | 2007-12-17 | 2009-06-25 | Siemens Healthcare Diagnostics Inc. | Methylation markers for cancer |
US20140274757A1 (en) | 2013-03-14 | 2014-09-18 | Marie K. Kirby | Differential Methylation Level of CpG Loci That Are Determinative of a Biochemical Reoccurrence of Prostate Cancer |
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US5411860A (en) * | 1992-04-07 | 1995-05-02 | The Johns Hopkins University | Amplification of human MDM2 gene in human tumors |
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1994
- 1994-11-15 US US08/340,203 patent/US5756668A/en not_active Expired - Lifetime
-
1995
- 1995-05-25 US US08/452,427 patent/US5922590A/en not_active Expired - Lifetime
- 1995-05-25 US US08/452,567 patent/US5846712A/en not_active Expired - Lifetime
- 1995-11-15 CN CN95197251A patent/CN1171743A/zh active Pending
- 1995-11-15 JP JP8516351A patent/JPH10510145A/ja active Pending
- 1995-11-15 NZ NZ298554A patent/NZ298554A/xx unknown
- 1995-11-15 CA CA002205414A patent/CA2205414A1/en not_active Abandoned
- 1995-11-15 EP EP95942863A patent/EP0792168A4/en not_active Withdrawn
- 1995-11-15 KR KR1019970703250A patent/KR970706849A/ko not_active Application Discontinuation
- 1995-11-15 AU AU44071/96A patent/AU4407196A/en not_active Abandoned
- 1995-11-15 WO PCT/US1995/014996 patent/WO1996014877A1/en not_active Application Discontinuation
- 1995-11-15 BR BR9509674A patent/BR9509674A/pt not_active Application Discontinuation
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1997
- 1997-05-14 NO NO972228A patent/NO972228L/no not_active Application Discontinuation
- 1997-05-14 FI FI972066A patent/FI972066A/fi unknown
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Also Published As
Publication number | Publication date |
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BR9509674A (pt) | 1997-09-16 |
FI972066A (fi) | 1997-07-14 |
CA2205414A1 (en) | 1996-05-23 |
US6103877A (en) | 2000-08-15 |
EP0792168A1 (en) | 1997-09-03 |
FI972066A0 (fi) | 1997-05-14 |
US5846712A (en) | 1998-12-08 |
US5756668A (en) | 1998-05-26 |
AU4407196A (en) | 1996-06-06 |
NO972228L (no) | 1997-07-14 |
MX9703582A (es) | 1997-10-31 |
JPH10510145A (ja) | 1998-10-06 |
WO1996014877A1 (en) | 1996-05-23 |
EP0792168A4 (en) | 1999-10-20 |
CN1171743A (zh) | 1998-01-28 |
NZ298554A (en) | 2000-01-28 |
US5922590A (en) | 1999-07-13 |
NO972228D0 (no) | 1997-05-14 |
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