Detection of novel germline mutations in six breast cancer predisposition genes by targeted next-generation sequencing

作者：Dong, Li; Wu, Nan; Wang, Shaojing; Cheng, Yanan; Han, Lei; Zhao, Jing; Long, Xinxin; Mu, Kun; Li, Menghui; Wei, Lijuan; Wang, Wanheng; Zhang, Weijia; Cao, Yandong; Liu, Juntian^*; Yu, Jinpu^*; Hao, Xishan

来源：Human Mutation, 2018, 39(10): 1442-1455.

DOI：10.1002/humu.23597

• breast cancer
• next-generation sequencing
• predisposition gene
• germline mutation
• clinical-pathological features

In this study, a customized amplicon-based target sequencing panel was designed to enrich the whole exon regions of six genes associated with the risk of breast cancer. Targeted next-generation sequencing (NGS) was performed for 146 breast cancer patients (BC), 71 healthy women with a family history of breast cancer (high risk), and 55 healthy women without a family history of cancer (control). Sixteen possible disease-causing mutations on four genes were identified in 20 samples. The percentages of possible disease-causing mutation carriers in the BC group (8.9%) and in the high-risk group (8.5%) were higher than that in the control group (1.8%). The BRCA1 possible disease-causing mutation group had a higher prevalence in family history and triple-negative breast cancer, while the BRCA2 possible disease-causing mutation group was younger and more likely to develop axillary lymph node metastasis (P<0.05). Among the 146 patients, 47 with a family history of breast cancer were also sequenced with another 14 moderate-risk genes. Three additional possible disease-causing mutations were found on PALB2, CHEK2, and PMS2 genes, respectively. The results demonstrate that the six-gene targeted NGS panel may provide an approach to assess the genetic risk of breast cancer and predict the clinical prognosis of breast cancer patients.

• 出版日期2018-10
• 单位天津医科大学