title: Lack of germ-line promoter methylation in BRCA1-negative families with familial breast cancer.
abstract: Hereditary breast cancer accounts for about 10% of breast cancer in the United States, but high-penetrance, germ-line mutations in BRCA1 and BRCA2 are responsible for less than half of these high-risk families. Epigenetic modification of DNA by promoter methylation can result in a potentially heritable epimutation that silences the gene. Using a highly sensitive technique, we assayed the BRCA1 gene for promoter methylation among 41 BRCA1- and BRCA2-negative women whose personal and family histories indicated a high risk of BRCA mutations (median prior likelihood = 60%) using the BRCAPro model. DNA from 19 women who were "true negatives" for BRCA mutations served as controls. We found no evidence for promoter methylation among the high-risk women who tested negative for germ-line BRCA mutations. Thus, epimutation is an unlikely explanation for hereditary breast cancer in women who test negative for BRCA mutations.
authors.affiliation: Department of Neurological Surgery, UCSF Comprehensive Cancer Center, San Francisco, California 9443-0875, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Toland
authors.forename: Jane
authors.initials: J
authors.lastname: McLennan
authors.forename: Jane
authors.initials: J
authors.lastname: Fridlyand
authors.forename: Beth
authors.initials: B
authors.lastname: Crawford
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Costello
authors.forename: John L
authors.initials: JL
authors.lastname: Ziegler
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D019175:DNA Methylation; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D011401:Promoter Regions, Genetic