Characterization of the genomic landscape and actionable mutations in Chinese breast cancers by clinical sequencing
Guan‐Tian Lang, Yi‐Zhou Jiang, Jinxiu Shi, Fan Yang, Xiaoguang Li, Yu‐Chen Pei, Chenhui Zhang, Ding Ma, Yi Xiao, Peng-Chen Hu, Hai Wang, Yun‐Song Yang, Linwei Guo, Xun‐Xi Lu, Mengzhu Xue, Peng Wang, A‐Yong Cao, Hong Ling, Zhonghua Wang, Ke‐Da Yu, Gen‐Hong Di, Da‐Qiang Li, Yun-Jin Wang, Ying Yu, Leming Shi, Xin Hu, Wei Huang, Zhi‐Ming Shao
Abstract
The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that NF2 loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer.