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Comparative Study
. 2020 Mar 12;20(1):204.
doi: 10.1186/s12885-020-6693-y.

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

Kyung Jin Eoh  1   2 , Hye Min Kim  3 , Jung-Yun Lee  2 , Sunghoon Kim  2 , Sang Wun Kim  2 , Young Tae Kim  2 , Eun Ji Nam  4   5
Affiliations
Comparative Study

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

Kyung Jin Eoh et al. BMC Cancer. .

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.

Keywords: BRCA1/2 mutation; High-grade serous ovarian cancer; Next-generation sequencing; Poly (ADP-ribose) polymerase.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Comparison of survival between overall BRCA mutation and BRCA wild-type in the Kaplan-Meier curve. BRCAm, BRCA mutation; BRCAw, BRCA wild-type
Fig. 2
Fig. 2
Distribution of germline and somatic BRCA1/2 mutations. Pts, patients
Fig. 3
Fig. 3
Landscape of somatic mutations and germline BRCA1/2 mutations in 98 patients with HGSOC. HGSOC, high-grade serous ovarian cancer
See this image and copyright information in PMC

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