• Ji Soo Park, Seung-Tae Lee, Eun Ji Nam, Jung Woo Han, Jung-Yun Lee, Jieun Kim, Tae Il Kim, and Hyung Seok Park.
• Hereditary Cancer Clinic, Cancer Prevention Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
• Bmc Cancer. 2018 Jan 16; 18 (1): 83.

BackgroundWe evaluated the incidence and spectrum of pathogenic and likely pathogenic variants of cancer susceptibility genes in BRCA1/2 mutation-negative Korean patients with a high risk for hereditary breast cancer using a comprehensive multigene panel that included 35 cancer susceptibility genes.MethodsSamples from 120 patients who were negative for BRCA1/2 mutations, but had been diagnosed with breast cancer that was likely hereditary, were prospectively evaluated for the prevalence of high-penetrance and moderate-penetrance germline mutations.ResultsNine patients (7.5%) had at least one pathogenic or likely pathogenic variant. Ten variants were identified in these patients: TP53 in two patients, PALB2 in three patients, BARD1 in two patients, BRIP1 in two patients, and MRE11A in one patient. We also identified 30 types of 139 variants of unknown significance (VUS). High-penetrance germline mutations, including TP53 and PALB2, tended to occur with high frequency in young (< 35 years) breast cancer patients (4/19, 21.1%) than in those diagnosed with breast cancer at ≥35 years of age (1/101, 1.0%; p = 0.003).ConclusionsThese combined results demonstrate that multigene panels offer an alternative strategy for identifying veiled pathogenic and likely pathogenic mutations in breast cancer susceptibility genes.

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