title: Promoter methylation patterns of ATM, ATR, BRCA1, BRCA2 and p53 as putative cancer risk modifiers in Jewish BRCA1/BRCA2 mutation carriers.
abstract: BRCA1/BRCA2 germline mutations substantially increase breast and ovarian cancer risk, yet penetrance is incomplete. We hypothesized that germline epigenetic gene silencing may affect mutant BRCA1/2 penetrance. To test this notion, we determined the methylation status, using methylation-specific quantitative PCR of the promoter in putative modifier genes: BRCA1, BRCA2, ATM, ATR and P53 in Jewish BRCA1/BRCA2 mutation carriers with (n = 41) or without (n = 48) breast cancer, in sporadic breast cancer (n = 52), and healthy controls (n = 89). Promoter hypermethylation was detected only in the BRCA1 promotor in 5.6-7.3% in each of the four subsets of participants, regardless of health and BRCA1/2 status.Germline promoter hypermethylation in the BRCA1 gene can be detected in about 5% of the female Israeli Jewish population, regardless of the BRCA1/2 status. The significance of this observation is yet to be determined.
authors.affiliation: The Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, The Chaim Sheba medical Center, Tel-Hashomer, Israel.
authors.forename: Tair
authors.initials: T
authors.lastname: Kontorovich
authors.forename: Yoram
authors.initials: Y
authors.lastname: Cohen
authors.forename: Uri
authors.initials: U
authors.lastname: Nir
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
mesh_terms: D000328:Adult; D000367:Age Factors; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007557:Israel; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000208:ethnology / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases