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Mutation landscape of germline and somatic BRCA1/2 in patients with high-grade serous ovarian cancer

Authors
 Kyung Jin Eoh  ;  Hye Min Kim  ;  Jung-Yun Lee  ;  Sunghoon Kim  ;  Sang Wun Kim  ;  Young Tae Kim  ;  Eun Ji Nam 
Citation
 BMC CANCER, Vol.20(1) : 204, 2020 
Journal Title
 BMC CANCER 
Issue Date
2020
Keywords
BRCA1/2 mutation ; High-grade serous ovarian cancer ; Next-generation sequencing ; Poly (ADP-ribose) polymerase
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.
Files in This Item:
T202000896.pdf Download
DOI
10.1186/s12885-020-6693-y
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sang Wun(김상운) ORCID logo https://orcid.org/0000-0002-8342-8701
Kim, Sung Hoon(김성훈) ORCID logo https://orcid.org/0000-0002-1645-7473
Kim, Young Tae(김영태) ORCID logo https://orcid.org/0000-0002-7347-1052
Kim, Hye Min(김혜민) ORCID logo https://orcid.org/0000-0002-2899-9480
Nam, Eun Ji(남은지) ORCID logo https://orcid.org/0000-0003-0189-3560
Eoh, Kyung Jin(어경진) ORCID logo https://orcid.org/0000-0002-1684-2267
Lee, Jung-Yun(이정윤) ORCID logo https://orcid.org/0000-0001-7948-1350
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/175643
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