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.

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

Cancer Molecular Diagnostics Core;The Second Department of Breast Cancer;Cancer Prevention Center,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin,Tianjin's Clinical Research Center for Cancer,Key Laboratory of Breast Cancer Prevention and Therapy,Tianjin Medical University,Ministry of Education,Tianjin 300060,China;Department of Oncology,Tianjin Third Central Hospital,Tianjin Institute of Hepatobiliary Disease,Tianjin Key Laboratory of Artificial Cell,Artificial Cell Engineering Technology Research Center of Public Health Ministry,Tianjin 300170,China;Analyses Technology Co.Ltd.,Beijing 102600,China

癌症生物学与医学（英文版）

[1]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-.The mutation landscape of multiple cancer predisposition genes in Chinese familial/hereditary breast cancer families)[J].癌症生物学与医学（英文版）,2022(06):850-870

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