Cancer Molecular Diagnostics Core, 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.
The Second Department of Breast Cancer, 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.
Cancer Biol Med. 2021 Sep 28;19(6):850-70. doi: 10.20892/j.issn.2095-3941.2021.0011.
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.
Ion Torrent S5™-based next generation sequencing was conducted on 116 subjects from 27 Chinese familial BC families.
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 genes, while 22.2% of the BC families exhibited defects in genes. In all, 41.7% (40/96) of the mutation carriers had mutations, 88.5% (85/96) had mutations, and 30.2% (29/96) had both and mutations. The BC patients with mutations had a higher risk of axillary lymph node metastases than those without mutations ( < 0.05). However, the BC patients with mutations frequently had a higher occurrence of benign breast diseases than those without mutations ( < 0.05).
In addition to , genetic variants in 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.
约 5%-10%的乳腺癌（BC）患者表现出家族特征，这些特征在家族成员中具有遗传性质。本研究的目的是分析 43 个具有不同外显率的种系基因突变，并探讨其与中国家族性 BC 家系表型特征的相关性。
对 27 个中国家族性 BC 家系的 116 名受试者进行基于 Ion Torrent S5™的下一代测序。
在 116 例病例中，82.8%（96/116）确定了 27 个 BC 易感性基因中的 81 个种系突变。其中，80.8%的突变基因与 DNA 损伤修复有关。在 27 个 BC 家系中，有 13 个家系发现了 14 个可能的致病变异。只有 25.9%（27/116）的 BC 家系存在基因遗传性缺陷，而 22.2%的 BC 家系存在基因缺陷。总的来说，41.7%（40/96）的突变携带者有突变，88.5%（85/96）有突变，30.2%（29/96）既有突变又有突变。与无突变相比，携带突变的 BC 患者腋窝淋巴结转移的风险更高（<0.05）。然而，与无突变相比，携带突变的 BC 患者良性乳腺疾病的发生率更高（<0.05）。
除了以外，DNA 修复基因中的遗传变异可能在家族性/遗传性 BC 的发生发展中发挥重要作用。因此，对多个 BC 易感性基因进行分析可能更有助于在中国家族性/遗传性 BC 中筛选潜在的致病性种系突变。
