Detection of Germline Mutations in Patients with Epithelial Ovarian Cancer Using Multi-gene Panels: Beyond BRCA1/2.
- Author:
Kyung Jin EOH
1
;
Ji Eun KIM
;
Hyung Seok PARK
;
Seung Tae LEE
;
Ji Soo PARK
;
Jung Woo HAN
;
Jung Yun LEE
;
Sunghoon KIM
;
Sang Wun KIM
;
Jae Hoon KIM
;
Young Tae KIM
;
Eun Ji NAM
Author Information
- Publication Type:Original Article
- Keywords: Ovarian epithelial cancer; Ethnicity; Germ-line mutation; Next-generation sequencing; Prevalence
- MeSH: Breast; Germ-Line Mutation*; Humans; Ovarian Neoplasms*; Prevalence
- From:Cancer Research and Treatment 2018;50(3):917-925
- CountryRepublic of Korea
- Language:English
- 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.
