Abstract 2508: Genomic alterations of BRCA1/2 genes in Chinese solid tumor patients

Abstract

Abstract Background: BRCA1 and BRCA2 are tumor suppressor genes that play an important role in DNA repair pathways. Germline mutations in BRCA1 and BRCA2 contribute to a significant number of familial and hereditary breast and/or ovarian cancers. Additionally, BRCA 1/2 alterations induce sensitivity to poly ADP ribose polymerase inhibitors (PARPi). Therefore, the detection of BRCA 1/2 mutations in solid tumor patients is essential to predict the sensitivity to PARPi therapy. Methods: FFPE tumor and matched blood samples of 5269 Chinese patients with solid tumor were collected for next generation sequencing (NGS) based assay. Genomic alterations including single nucleotide variations (SNV), short and long insertions/deletions (Indel), copy number variations (CNV) and gene rearrangements and fusions in selected genes were assessed. Results: Three hundred patients with BRCA1/2 mutations were identified in 5269 Chinese patients with solid tumor. The patients included 177 males and 123 females with a median age of 58. Highest yields of BRCA1/2 mutations were found in patients with ovarian (24.5%) and breast (12.3%) cancers. BRCA1/2 mutations were also identified in gastric cancer (8.9%), cholangiocarcinoma (8.8%), colorectal cancer (7.1%), esophageal cancer (6.1%), gallbladder cancer (5.1%), lung cancer (4.7%), soft tissue tumor (4.1%) and pancreatic cancer (4.0%). SNVs and short Indels (84.9%) were the most common variant types of BRCA1/2, while the percentages of gene rearrangements and fusions, CNV and long Indels were 12.0%, 1.6% and 1.5%, respectively. Among patients with BRCA1/2 mutations, 224 (74.7%) patients harbored somatic mutations, 73 (24.3%) patients harbored germline mutations, 3 (1.0%) patients harbored both somatic and germline mutations. Interestingly, all of the variant types of germline mutations were SNVs and short Indels. The mutation sites were distributed in the full length of BRCA1/2 genes. No hot spot mutation was observed. Conclusions: Our data revealed that BRCA1/2 mutations occurred in 5.7% of Chinese patients with solid tumor. NGS targeted sequencing provides comprehensive and accurate information of BRCA1/2 mutations. Beyond ovarian and breast cancers, BRCA1/2 mutations could be detected in other solid tumors, which suggests potential clinical benefits from PARPi therapy. Citation Format: Junjian Wang, Lingxiang Liu, Bin Ni, Xiaoqian Chen, Ling Li, Junping Shi, Jierong Chen, Ming Yao. Genomic alterations of BRCA1/2 genes in Chinese solid tumor patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2508.