245P - Frequency of germline mutations in women’s cancer susceptibility genes in a large cohort of Chinese breast cancer patients

Abstract

BackgroundThe prevalence of cancer related germline mutations in unselected Chinese breast cancer (BC) patients is unknown. Our study aims to examine the germline mutations prevalence and to investigate the relationship among tumor characteristics, somatic mutations and germline mutations. MethodsMatched white blood cells and tumor tissue samples of 524 unselected Chinese BC patients (stage Tis to IV) were profiled using a panel consisting of 520 cancer-related genes. Germline mutations of 62 cancer susceptibility genes included all breast/ovarian cancer-related genes in the US genetic guidelines were assessed. ResultsA total of 76 pathogenic or likely pathogenic (P/LP) germline variants spanning 15 genes were detected from 58 patients (11%), with 29 and 38 mutations detected in BRCA1/2 and other cancer susceptibility genes, respectively. Overall, mutations detected included 11 BRCA1, 18 BRCA2, 4 MUTYH, 4 PALB2, 3ATM, 3 BRIP1, 3 CDH1, 3 RAD51C, 2 CHEK2, 2 FANCA, 2 PMS2, 2 TP53, 1 FANCI, 1 FANCL and 1 PTEN. We detected 1968 germline mutations classified as variants of uncertain significance spanning all 62 cancer susceptibility genes from 490 patients (93%). We revealed young age, premenopausal status, and family history of breast/ovarian cancer were associated with P/LP germline mutations. Interestingly, somatic TP53 mutations were detected in all patients with P/LP germline BRCA1 mutations (100%, 11/11) and a majority (67%, 2/3) of patients with likely pathogenic CDH1 mutations. No somatic TP53 mutation was detected in patients with germline ATM and TP53 mutations. Somatic PIK3CA mutations were more frequently seen in patients with germline CDH1 (3/3). A patient with pathogenic germline PALB2 mutation (p.Q921fs) also has somatic PALB2 mutation (p.D525fs). ConclusionsOur study derived the prevalence of P/LP germline mutation in 524 Chinese BC patients and 11% were found to have a germline mutation. We explored the characteristics of tumor somatic mutations in germline mutations carriers, which provided a better understanding of patients with germline mutations. Legal entity responsible for the studyNing Liao. FundingNational Natural Science Foundation of China (Grant No. 81602645), Guangdong Provincial Natural Science Foundation (Grant No. 2016A030313768). DisclosureAll authors have declared no conflicts of interest.