Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer

Autor: Yi Zhang, Yan Xu, Chong-Jian Chen, Jianjun He, Fuguo Tian, Jianguo Zhang, Fan Zhang, Rui Ling, Xinhua Yang, Liang Junbin, Xiangjun Cai, Yuan Sheng, Jiang-Hua Ou, Rui-Shan Zhang, Jing BoLi, Ai-Hua Guan, Hengyu Li, Ping Shuai, Hongchuan Jiang, Weiwei Huang, Hong Xu, Zhenzhen Liu, Baoliang Guo, Minghao Wang, Qinwen Pan, Qi Xiaowei, Junyan Li, Jing Ruilin, Jun Jiang, Xuan Zhaoling, Hongyi Wei, Jia Ming, Chun-Yan Hu, Ling Zhong, Linjun Fan, Li Chen, Xuanni Tan, Zhen Zeng, Ning Liao, Haoxi Liu, Ke Liu, Liu Jian, Ting Zhang, Lizhi Ouyang, Weihua Jiang, Yu Ren
Rok vydání: 2018
Předmět:
Zdroj: International Journal of Cancer. 144:281-289
ISSN: 0020-7136
Popis: Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.
Databáze: OpenAIRE
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