1. Mutation landscape of germline and somatic BRCA1/2 in patients with high-grade serous ovarian cancer
- Author
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Hye Min Kim, Sunghoon Kim, Kyung Jin Eoh, Sang Wun Kim, Jung Yun Lee, Young Tae Kim, and Eun Ji Nam
- Subjects
Adult ,Cancer Research ,endocrine system diseases ,Somatic cell ,Biology ,Poly(ADP-ribose) Polymerase Inhibitors ,medicine.disease_cause ,lcsh:RC254-282 ,DNA sequencing ,Germline ,03 medical and health sciences ,symbols.namesake ,Young Adult ,0302 clinical medicine ,Germline mutation ,Genetics ,medicine ,Humans ,030212 general & internal medicine ,Poly (ADP-ribose) polymerase ,Germ-Line Mutation ,Aged ,Sanger sequencing ,BRCA2 Protein ,Ovarian Neoplasms ,Mutation ,BRCA1 Protein ,Cancer ,High-Throughput Nucleotide Sequencing ,BRCA1/2 mutation ,Sequence Analysis, DNA ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cystadenocarcinoma, Serous ,DNA-Binding Proteins ,Oncology ,030220 oncology & carcinogenesis ,Mutation testing ,Cancer research ,symbols ,Next-generation sequencing ,Female ,Neoplasm Grading ,High-grade serous ovarian cancer ,Research Article ,Transcription Factors - Abstract
Background Poly (ADP-ribose) polymerase inhibitors targeting BRCA1/2 mutations are available for treating patients with high-grade serous ovarian cancer. These treatments may be more appropriately directed to patients who might respond if the tumor tissue is additionally tested by next-generation sequencing with a multi-gene panel and Sanger sequencing of a blood sample. In this study, we compared the results obtained using the next-generation sequencing multi-gene panel to a known germline BRCA1/2 mutational state determined by conventional Sanger sequencing to evaluate the landscape of somatic mutations in high-grade serous ovarian cancer tumors. Methods Cancer tissue from 98 patients with high-grade serous ovarian cancer who underwent Sanger sequencing for germline BRCA1/2 analysis were consecutively analyzed for somatic mutations using a next-generation sequencing 170-gene panel. Results Twenty-four patients (24.5%) showed overall BRCA1/2 mutations. Seven patients (7.1%) contained only somatic BRCA1/2 mutations with wild-type germline BRCA1/2, indicating acquired mutation of BRCA1/2. Three patients (3.1%) showed reversion of germline BRCA1 mutations. Among the 14 patients (14.3%) with both germline and somatic mutations in BRCA1/2, two patients showed different variations of BRCA1/2 mutations. The next-generation sequencing panel test for somatic mutation detected other pathogenic variations including RAD51D and ARID1A, which are possible targets of poly (ADP-ribose) polymerase inhibitors. Compared to conventional Sanger sequencing alone, next-generation sequencing-based tissue analysis increased the number of candidates for poly (ADP-ribose) polymerase inhibitor treatment from 17.3% (17/98) to 26.5% (26/98). Conclusions Somatic mutation analysis by next-generation sequencing, in addition to germline BRCA1/2 mutation analysis, should become the standard of care for managing women with high-grade serous ovarian cancer to widen the indication of poly (ADP-ribose) polymerase inhibitors.
- Published
- 2020