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BMC Cancer. 2018 Jan 16;18(1):83. doi: 10.1186/s12885-017-3940-y.

Variants of cancer susceptibility genes in Korean BRCA1/2 mutation-negative patients with high risk for hereditary breast cancer.

Park JS1, Lee ST1,2, Nam EJ1,3, Han JW1,4, Lee JY1,3, Kim J5, Kim TI1,6, Park HS7,8.

Author information

1
Hereditary Cancer Clinic, Cancer Prevention Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
2
Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
3
Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Women's Cancer Clinic, Yonsei University College of Medicine, Seoul, Republic of Korea.
4
Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea.
5
Department of Laboratory Medicine, Soonchunhyang University School of Medicine, Seoul, Republic of Korea.
6
Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
7
Hereditary Cancer Clinic, Cancer Prevention Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. hyungseokpark.md@gmail.com.
8
Department of Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. hyungseokpark.md@gmail.com.

Abstract

BACKGROUND:

We 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.

METHODS:

Samples 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.

RESULTS:

Nine 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).

CONCLUSIONS:

These combined results demonstrate that multigene panels offer an alternative strategy for identifying veiled pathogenic and likely pathogenic mutations in breast cancer susceptibility genes.

KEYWORDS:

Beyond BRCA1/2; Breast neoplasms; Multigene panel; Neoplastic Syndromes, Hereditary; Next generation sequencing

PMID:
29338689
PMCID:
PMC5769462
DOI:
10.1186/s12885-017-3940-y
[Indexed for MEDLINE]
Free PMC Article

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