rad51c germline mutations in breast and ovarian cancer cases from high-risk familiesrad51c遗传突变在乳腺癌和卵巢癌的情况下从高风险的家庭.pdfVIP

RAD51C Germline Mutations in Breast and Ovarian Cancer Cases from High-Risk Families 1. 2. 2 3 1 Jessica Clague , Greg Wilhoite , Aaron Adamson , Adam Bailis , Jeffrey N. Weitzel , Susan L. Neuhausen2* 1 Division of Clinical Cancer Genetics, Beckman Research Institute at the City of Hope National Medical Center, Duarte, California, United States of America, 2 Department of Population Sciences, Beckman Research Institute at the City of Hope National Medical Center, Duarte, California, United States of America, 3 Department of Molecular and Cellular Biology, Beckman Research Institute at the City of Hope National Medical Center, Duarte, California, United States of America Abstract BRCA1 and BRCA2 are the most well-known breast cancer susceptibility genes. Additional genes involved in DNA repair have been identified as predisposing to breast cancer. One such gene, RAD51C, is essential for homologous recombination repair. Several likely pathogenic RAD51C mutations have been identified in BRCA1- and BRCA2-negative breast and ovarian cancer families. We performed complete sequencing of RAD51C in germline DNA of 286 female breast and/or ovarian cancer cases with a family history of breast and ovarian cancers, who had previously tested negative for mutations in BRCA1 and BRCA2. We screened 133 breast cancer cases, 119 ovarian cancer cases, and 34 with both breast and ovarian cancers. Fifteen DNA sequence variants were identified; including four intronic, one 59 UTR, one promoter, three synonymous, and six non-synonymous variants. None were truncating. The in-silico SIFT and Polyphen programs were used to predict possible pathogenicity of the six non-synonomous variants based