Somatic mutations in triple-negative breast carcinoma and high-grade serous ovarian carcinoma from young women.

Abstract

e12561 Background: High grade serous ovarian carcinoma (HGSOvCa) and triple negative breast cancer (TNBC) share characteristics, such as poor prognosis, BRCA1 germline mutations and TP53 somatic mutations. Our aim was to analyze somatic mutations from HGS-OvCa and TNBC from young patients aged ≤ 40 years. Methods: Whole genome or exome sequencing data for TNBC (n = 83) or HGS-OvCa (n = 21) was recovered from COSMIC or cBioPortal. Data was searched for cancer driver genes catalogued in Cancer Gene Census (CGC) or Candidate Cancer Gene Database rank A or B (CCGD) and for DNA repair genes. Results: TNBC mainly consisted of ductal carcinomas (78/83). A median of two cancer causing genes was affected in both TNBC and HGS-OvCa and TP53 was mutated in at least 2/3 of the samples. Only 7/83 and 2/19 of TNBC and HGS-OvCa samples, respectively, did not present variants in known cancer causing genes. C > T substitutions were the most frequent events in both TNBC and HGS-OvCa, however transversions were more frequently detected in TNBC. Besides TP53, another 33 genes were mutated in both tumor types, including PIK3CA, RYR2, TARBP1, CSMD3, DNAH11, MYO3A, NF1, TNRC6A, CACNA1E, HCMN1, PRKDC. Conclusions: Although many similarities were detected, TNBC in young patients presents a higher number of transversions and almost 25% of HGSOvCa present somatic mutations in HR genes. [Table: see text]