Characterization of the genomic landscape and actionable mutations in Chinese breast cancers by clinical sequencing

Guan-Tian Lang, Yi-Zhou Jiang, Jin-Xiu Shi, Fan Yang, Xiao-Guang Li, Yu-Chen Pei, Chen-Hui Zhang, Ding Ma, Yi Xiao, Peng-Chen Hu, Hai Wang, Yun-Song Yang, Lin-Wei Guo, Xun-Xi Lu, Meng-Zhu Xue, Peng Wang, A-Yong Cao, Hong Ling, Zhong-Hua Wang, Ke-Da Yu, Gen-Hong Di, Da-Qiang Li, Yun-Jin Wang, Ying Yu, Le-Ming Shi, Xin Hu (), Wei Huang () and Zhi-Ming Shao ()
Additional contact information
Guan-Tian Lang: Fudan University Shanghai Cancer Center
Yi-Zhou Jiang: Fudan University Shanghai Cancer Center
Jin-Xiu Shi: Chinese National Human Genome Center at Shanghai (CHGC) and Shanghai Academy of Science and Technology (SAST)
Fan Yang: Fudan University Shanghai Cancer Center
Xiao-Guang Li: Fudan University Shanghai Cancer Center
Yu-Chen Pei: Fudan University Shanghai Cancer Center
Chen-Hui Zhang: Chinese National Human Genome Center at Shanghai (CHGC) and Shanghai Academy of Science and Technology (SAST)
Ding Ma: Fudan University Shanghai Cancer Center
Yi Xiao: Fudan University Shanghai Cancer Center
Peng-Chen Hu: Chinese National Human Genome Center at Shanghai (CHGC) and Shanghai Academy of Science and Technology (SAST)
Hai Wang: Fudan University Shanghai Cancer Center
Yun-Song Yang: Fudan University Shanghai Cancer Center
Lin-Wei Guo: Fudan University Shanghai Cancer Center
Xun-Xi Lu: Fudan University Shanghai Cancer Center
Meng-Zhu Xue: Chinese Academy of Sciences
Peng Wang: Chinese Academy of Sciences
A-Yong Cao: Fudan University Shanghai Cancer Center
Hong Ling: Fudan University Shanghai Cancer Center
Zhong-Hua Wang: Fudan University Shanghai Cancer Center
Ke-Da Yu: Fudan University Shanghai Cancer Center
Gen-Hong Di: Fudan University Shanghai Cancer Center
Da-Qiang Li: Fudan University Shanghai Cancer Center
Yun-Jin Wang: Fudan University Shanghai Cancer Center
Ying Yu: Fudan University
Le-Ming Shi: Fudan University
Xin Hu: Fudan University Shanghai Cancer Center
Wei Huang: Chinese National Human Genome Center at Shanghai (CHGC) and Shanghai Academy of Science and Technology (SAST)
Zhi-Ming Shao: Fudan University Shanghai Cancer Center

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19342-3

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