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. 2018 Jul;50(3):917-925.
doi: 10.4143/crt.2017.220. Epub 2017 Sep 27.

Detection of Germline Mutations in Patients with Epithelial Ovarian Cancer Using Multi-gene Panels: Beyond BRCA1/2

Kyung Jin Eoh  1   2 , Ji Eun Kim  1   3 , Hyung Seok Park  1   4 , Seung-Tae Lee  1   3 , Ji Soo Park  1   5 , Jung Woo Han  1   6 , Jung-Yun Lee  1   2 , Sunghoon Kim  1   2 , Sang Wun Kim  1   2 , Jae Hoon Kim  7 , Young Tae Kim  1   2 , Eun Ji Nam  1   2
Affiliations

Detection of Germline Mutations in Patients with Epithelial Ovarian Cancer Using Multi-gene Panels: Beyond BRCA1/2

Kyung Jin Eoh et al. Cancer Res Treat. 2018 Jul.

Abstract

Purpose: Next-generation sequencing (NGS) allows simultaneous sequencing of multiple cancer susceptibility genes and may represent a more efficient and less expensive approach than sequential testing. We assessed the frequency of germline mutations in individuals with epithelial ovarian cancer (EOC), using multi-gene panels and NGS.

Materials and methods: Patients with EOC (n=117) with/without a family history of breast or ovarian cancer were recruited consecutively, from March 2016 toDecember 2016.GermlineDNAwas sequenced using 35-gene NGS panel, in order to identify mutations. Upon the detection of a genetic alteration using the panel, results were cross-validated using direct sequencing.

Results: Thirty-eight patients (32.5%) had 39 pathogenic or likely pathogenic mutations in eight genes, including BRCA1 (n=21), BRCA2 (n=10), BRIP1 (n=1), CHEK2 (n=2), MSH2 (n=1), POLE (n=1), RAD51C (n=2), and RAD51D (n=2). Among 64 patients with a family history of cancer, 27 (42.2%) had 27 pathogenic or likely pathogenic mutations, and six (9.3%) had mutations in genes other than BRCA1/2, such as CHECK2, MSH2, POLE, and RAD51C. Fifty-five patients (47.0%) were identified to carry only variants of uncertain significance.

Conclusion: Using the multi-gene panel test, we found that, of all patients included in our study, 32.5% had germline cancer-predisposing mutations. NGS was confirmed to substantially improve the detection rates of a wide spectrum of mutations in EOC patients compared with those obtained with the BRCA1/2 testing alone.

Keywords: Ethnicity; Germ-line mutation; Next-generation sequencing; Prevalence; Ovarian epithelial cancer.

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Conflict of interest statement

Conflict of interest relevant to this article was not reported.

Figures

Fig. 1.
Fig. 1.
Multiple-gene panel testing results. In a patient, multiple mutations were concomitantly identified. EOC, epithelial ovarian cancer; VOUS, variants of uncertain significance. a)Two mutations including BRCA1 and one non-BRCA1/2 gene were identified simultaneously in a patient.
Fig. 2.
Fig. 2.
Proportion of pathogenic or likely pathogenic mutations and variants of uncertain significance (VOUSs). (A) Multigene panel test results. (B) Proportion and number of pathogenic or likely pathogenic mutations.
Fig. 3.
Fig. 3.
Frequency and spectrum of variants of unknown significance in cancer susceptibility genes.
See this image and copyright information in PMC

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