Identification of germline mutation by 30 gene sequencing and clinical characteristics of Chinese with hereditary ovarian cancer

Abstract

Background and Aims: BRCA mutations attributed to 10-15% of hereditary ovarian cancers and are routinely tested in hereditary breast and ovarian cancers (HBOC). However, mutation prevalence of other HBOC genes has not been well-studied in Chinese patients with ovarian cancer. Methods: 398 ovarian cancer patients joined the Hong Kong Hereditary Breast Cancer Family Registry were subjected to 6-gene panel (BRCA1, BRCA2, TP53, PTEN, PALB2 and CDH1) by next-generation sequencing (NGS) for molecular diagnosis. 82 high-risk patients who were negative for 6 genes were then subjected to a 30-gene panel by NGS (Color Genomics). All detectable pathogenic variants were further validated by bi-directional DNA sequencing. Results: Of 398 ovarian cancer patients, 43 (10.8%) BRCA1, 17 (4.27%) BRCA2 and 1 (0.25%) PALB2 pathogenic carriers were identified. Seven pathogenic variants in ATM, BARD1, MSH2, MSH6 and RAD51D were further identified by 30-gene panel. 60 (88.24%) of the pathogenic carriers have family history of cancers. Among these carriers, 40 (66.67%) of them have family history of breast and/or ovarian cancers. 67 (98.52%) of the pathogenic carriers were being diagnosed with epithelial ovarian cancers. Those diagnosed with combined ovarian and uterine/endometrial cancer, 6/48 (12.5%) carried mutated pathogenic genes with 3/6 (50%) are BRCA related. Conclusions: BRCA mutations are the most prevalent mutations in Chinese ovarian cancer patients with family history of cancers. The use of multigene panels identified additional 2% pathogenic variants. Implementation of multigene sequencing should be included in mutation screening to offer appropriate treatments or select patients to clinical trials in synchronous ovarian and uterine/endometrial cancer.