Abstract
Most breast cancer genomes harbor complex mutational landscapes. Somatic alterations have been predominantly discovered in breast cancer patients of European ancestry; however, little is known about somatic aberration in patients of other ethnic groups including Asians. In the present study, whole-exome sequencing (WES) was conducted in DNA extracted from tumor and matched adjacent normal tissue samples from eleven early onset breast cancer patients who were included in the Shanghai Breast Cancer Study. We discovered 159 somatic missense and ten nonsense mutations distributed among 167 genes. The most frequent 50 somatic mutations identified by WES were selected for validation using Sequenom MassARRAY system in the eleven breast cancer patients and an additional 433 tumor and 921 normal tissue/blood samples from the Shanghai Breast Cancer Study. Among these 50 mutations selected for validation, 32 were technically validated. Within the validated mutations, somatic mutations in the TRPM6, HYDIN, ENTHD1, and NDUFB10 genes were found in two or more tumor samples in the replication stage. Mutations in the ADRA1B, CBFB, KIAA2022, and RBM25 genes were observed once in the replication stage. To summarize, this study identified some novel somatic mutations for breast cancer. Future studies will need to be conducted to determine the function of these mutations/genes in the breast carcinogenesis.
Highlights
Breast cancer is the most common malignancy among women worldwide
We identified 588 mutations with 40% located in coding regions
Mutations in the PIK3CA, TRPM6, HYDIN, ENTHD1 and NDUFB10 genes were observed in multiple samples in the replication stage
Summary
Breast cancer is the most common malignancy among women worldwide. In the United States, there were 226,870 new cases diagnosed and 39,510 deaths in 2012 [1]. Breast cancer remains the second leading cause of female cancer mortality It is well-established that breast cancer genomes harbor complex mutational landscapes, often characterized by point mutations, small insertions and deletions (Indels), and large structure changes across the genome [2,3,4,5,6,7]. Such somatic DNA changes in the tumor genome may result in an inactivation of tumor suppressor genes and activation or deregulation of oncogenes. Comprehensive identification of these somatic changes is necessary to better understand biological mechanisms of carcinogenesis and cancer progression, which may help to predict prognosis and to advance the development of targeted therapies
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