The mutation landscape of multiple cancer predisposition genes in Chinese familial/hereditary breast cancer families

Autor: Li Dong, Hailian Zhang, Huan Zhang, Yingnan Ye, Yanan Cheng, Lijuan Li, Lijuan Wei, Lei Han, Yandong Cao, Shixia Li, Xishan Hao, Juntian Liu, Jinpu Yu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cancer Biology & Medicine, Vol 19, Iss 6, Pp 850-870 (2022)
Druh dokumentu: article
ISSN: 2095-3941
29876265
DOI: 10.20892/j.issn.2095-3941.2021.0011
Popis: Objective: Approximately 5%–10% of breast cancer (BC) patients display familial traits that are genetically inherited among the members of a family. The purpose of this study was to profile the germline mutations in 43 genes with different penetration rates and their correlations with phenotypic traits in Chinese familial BC families. Methods: Ion Torrent S5™-based next generation sequencing was conducted on 116 subjects from 27 Chinese familial BC families. Results: Eighty-one germline mutations in 27 BC predisposition genes were identified in 82.8% (96/116) of the cases. Among these, 80.8% of the mutated genes were related to DNA damage repair. Fourteen possible disease-causing variants were identified in 13 of 27 BC families. Only 25.9% (7/27) of the BC families exhibited hereditary deficiency in BRCA1/2 genes, while 22.2% of the BC families exhibited defects in non-BRCA genes. In all, 41.7% (40/96) of the mutation carriers had BRCA mutations, 88.5% (85/96) had non-BRCA mutations, and 30.2% (29/96) had both BRCA and non-BRCA mutations. The BC patients with BRCA mutations had a higher risk of axillary lymph node metastases than those without mutations (P < 0.05). However, the BC patients with non-BRCA mutations frequently had a higher occurrence of benign breast diseases than those without mutations (P < 0.05). Conclusions: In addition to BRCA1/2, genetic variants in non-BRCA DNA repair genes might play significant roles in the development of familial/hereditary BC. Therefore, profiling of multiple BC predisposition genes should be more valuable for screening potential pathogenic germline mutations in Chinese familial/hereditary BC.
Databáze: Directory of Open Access Journals
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