WO2009071920A3 - Methods for identifying epigenetically silenced genes and novel tumour suppressor genes - Google Patents

Methods for identifying epigenetically silenced genes and novel tumour suppressor genes Download PDF

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Publication number
WO2009071920A3
WO2009071920A3 PCT/GB2008/004045 GB2008004045W WO2009071920A3 WO 2009071920 A3 WO2009071920 A3 WO 2009071920A3 GB 2008004045 W GB2008004045 W GB 2008004045W WO 2009071920 A3 WO2009071920 A3 WO 2009071920A3
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cancer
gene
expression
protein
activity
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PCT/GB2008/004045
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French (fr)
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WO2009071920A2 (en
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Manuel Esteller
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Oncomethylome Sciences Sa
Spencer, Matthew, Peter
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Publication of WO2009071920A3 publication Critical patent/WO2009071920A3/en

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    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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Abstract

A method of detecting a predisposition to, or the incidence of, cancer in a sample comprises detecting an epigenetic change in at least one gene selected from PARVG, FGF19, PTPRN, COL11A2 and LTBP3, wherein detection of the epigenetic change is indicative of a predisposition to, or the incidence of, cancer. The cancer may be lung cancer, cervical cancer, breast cancer, colon cancer, leukaemia or lymphoma. Related methods and kits can also be employed to select suitable treatments for cancer, stage cancer and treat cancer. A method of treating cancer comprises inhibiting the expression or activity of at least one Methyl Binding Domain (MBD) gene or protein in tumour cells, thus alleviating epigenetic silencing of at least one tumour suppressor gene. A method for identifying at least one epigenetically silenced gene in a cell comprises either inhibiting the expression or activity of at least one MBD gene or protein in the cell and identifying one or more genes whose expression is upregulated as a result of inhibiting the expression or activity of the at least one MBD gene or protein in the cell; or, in a cell in which the expression or activity of at least one MBD gene or protein has been inhibited, identifying one or more genes whose expression is upregulated as a result of inhibiting the expression or activity of the at least one MBD gene or protein in the cell.
PCT/GB2008/004045 2007-12-07 2008-12-08 Methods for identifying epigenetically silenced genes and novel tumour suppressor genes WO2009071920A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US99685907P 2007-12-07 2007-12-07
US60/996.859 2007-12-07

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WO2009071920A2 WO2009071920A2 (en) 2009-06-11
WO2009071920A3 true WO2009071920A3 (en) 2009-10-29

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Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2012347263A1 (en) * 2011-12-09 2014-07-24 Mycartis N.V. LTBP2 as a biomarker for lung injury
CN104911260A (en) * 2015-04-28 2015-09-16 凯杰（苏州）转化医学研究有限公司 Novel detection kit for copy number of fibroblast growth factor 19 (FGF19) gene

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998000552A2 (en) * 1996-07-02 1998-01-08 President And Fellows Of Harvard College Receptor tyrosine phosphatase, and uses related thereto
WO2002070742A1 (en) * 2001-03-01 2002-09-12 Epigenomics Ag Method for the development of gene panels for diagnostic and therapeutic purposes based on the expression and methylatoin status of the genes
WO2004031402A2 (en) * 2002-10-02 2004-04-15 Northwestern University Methylation profile of cancer
US20040170977A1 (en) * 2000-03-31 2004-09-02 Peter Laird Epigenetic sequences for esophageal adenocarcinoma
US20070010469A1 (en) * 2000-06-02 2007-01-11 Chan Vivien W Gene products differentially expressed in cancerous cells III
WO2007009755A2 (en) * 2005-07-18 2007-01-25 Epigenomics Ag Compositions and methods for cancer diagnostics comprising pan-cancer markers

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998000552A2 (en) * 1996-07-02 1998-01-08 President And Fellows Of Harvard College Receptor tyrosine phosphatase, and uses related thereto
US20040170977A1 (en) * 2000-03-31 2004-09-02 Peter Laird Epigenetic sequences for esophageal adenocarcinoma
US20070010469A1 (en) * 2000-06-02 2007-01-11 Chan Vivien W Gene products differentially expressed in cancerous cells III
WO2002070742A1 (en) * 2001-03-01 2002-09-12 Epigenomics Ag Method for the development of gene panels for diagnostic and therapeutic purposes based on the expression and methylatoin status of the genes
WO2004031402A2 (en) * 2002-10-02 2004-04-15 Northwestern University Methylation profile of cancer
WO2007009755A2 (en) * 2005-07-18 2007-01-25 Epigenomics Ag Compositions and methods for cancer diagnostics comprising pan-cancer markers

Non-Patent Citations (15)

* Cited by examiner, † Cited by third party
Title
AURIOL EMILIE ET AL: "Specific binding of the methyl binding domain protein 2 at the BRCA1-NBR2 locus.", NUCLEIC ACIDS RESEARCH 2005, vol. 33, no. 13, 2005, pages 4243 - 4254, XP007908118, ISSN: 1362-4962 *
BALLESTAR E ET AL: "Methyl-CpG binding proteins identify novel sites of epigenetic inactivation in human cancer", EMBO JOURNAL, OXFORD UNIVERSITY PRESS, SURREY, GB, vol. 22, no. 23, 1 December 2003 (2003-12-01), pages 6335 - 6345, XP002996407, ISSN: 0261-4189 *
BALLESTAR ESTEBAN ET AL: "Methyl-CpG-binding proteins in cancer: blaming the DNA methylation messenger", BIOCHEMISTRY AND CELL BIOLOGY. BIOCHIMIE ET BIOLOGIE CELLULAIRE, NRC RESEARCH PRESS, CA, vol. 83, no. 3, 1 June 2005 (2005-06-01), pages 374 - 384, XP009115061, ISSN: 0829-8211 *
EADS C A ET AL: "Epigenetic patterns in the progression of esophageal adenocarcinoma", CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD.; US, vol. 61, no. 8, 15 April 2001 (2001-04-15), pages 3410 - 3418, XP002982118, ISSN: 0008-5472 *
ESTELLER M: "CpG island methylation and histone modifications: biology and clinical significance.", ERNST SCHERING RESEARCH FOUNDATION WORKSHOP 2006, no. 57, 2006, pages 115 - 126, XP009115191, ISSN: 0947-6075 *
GORE STEVEN D ET AL: "Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms", CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD.; US, vol. 66, no. 12, 15 June 2006 (2006-06-15), pages 6361 - 6369, XP002477180, ISSN: 0008-5472 *
HERRANZ MICHEL ET AL: "DNA methylation and histone modifications in patients with cancer: potential prognostic and therapeutic targets.", METHODS IN MOLECULAR BIOLOGY (CLIFTON, N.J.) 2007, vol. 361, 5 February 2007 (2007-02-05), pages 25 - 62, XP009115201, ISSN: 1064-3745 *
KORENBAUM E ET AL: "Genomic organization and expression profile of the parvin family of focal adhesion proteins in mice and humans", GENE, ELSEVIER, AMSTERDAM, NL, vol. 279, no. 1, 14 November 2001 (2001-11-14), pages 69 - 79, XP004324225, ISSN: 0378-1119 *
LIN XIAOHUI ET AL: "Methyl-CpG-binding domain protein-2 mediates transcriptional repression associated with hypermethylated GSTP1 CpG islands in MCF-7 breast cancer cells.", CANCER RESEARCH 15 JAN 2003, vol. 63, no. 2, 15 January 2003 (2003-01-15), pages 498 - 504, XP007908116, ISSN: 0008-5472 *
LODYGIN D ET AL: "Functional epigenomics identifies genes frequently silenced in prostate cancer", CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD.; US, vol. 65, no. 10, 1 May 2005 (2005-05-01), pages 4218 - 4227, XP002344096, ISSN: 0008-5472 *
LOPEZ-SERRA LIDIA ET AL: "A profile of methyl-CpG binding domain protein occupancy of hypermethylated promoter CpG islands of tumor suppressor genes in human cancer.", CANCER RESEARCH 1 SEP 2006, vol. 66, no. 17, 1 September 2006 (2006-09-01), pages 8342 - 8346, XP007908119, ISSN: 1538-7445 *
MIRZA ET AL: "Promoter hypermethylation of TMS1, BRCA1, ERalpha and PRB in serum and tumor DNA of invasive ductal breast carcinoma patients", LIFE SCIENCES, PERGAMON PRESS, OXFORD, GB, vol. 81, no. 4, 10 July 2007 (2007-07-10), pages 280 - 287, XP022145933, ISSN: 0024-3205 *
QINGHUA FENG ET AL: "Promoter Hypermethylation of Tumor Suppressor Genes in Urine from Patients with Cervical Neoplasia", CANCER EPIDEMIOLOGY, BIOMARKERS AND PREVENTION, PHILADELPHIA, PA, vol. 16, no. 6, 1 June 2007 (2007-06-01), pages 1178 - 1184, XP007908131, ISSN: 1055-9965 *
RAJ K ET AL: "CDKN2B methylation status and isolated chromosome 7 abnormalities predict responses to treatment with 5-azacytidine.", LEUKEMIA : OFFICIAL JOURNAL OF THE LEUKEMIA SOCIETY OF AMERICA, LEUKEMIA RESEARCH FUND, U.K SEP 2007, vol. 21, no. 9, September 2007 (2007-09-01), pages 1937 - 1944, XP007908151, ISSN: 0887-6924 *
SHIVAPURKAR ET AL: "Evaluation of candidate methylation markers to detect cervical neoplasia", GYNECOLOGIC ONCOLOGY, ACADEMIC PRESS, LONDON, GB, vol. 107, no. 3, 1 December 2007 (2007-12-01), pages 549 - 553, XP022405899, ISSN: 0090-8258 *

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