Characterization of PIK3CA and PIK3R1 somatic mutations in Chinese breast cancer patients

• Published in: Nature communications Vol. 9; no. 1; pp. 1357 - 17
• Main Authors: Chen, Li, Yang, Liu, Yao, Ling, Kuang, Xia-Ying, Zuo, Wen-Jia, Li, Shan, Qiao, Feng, Liu, Yi-Rong, Cao, Zhi-Gang, Zhou, Shu-Ling, Zhou, Xiao-Yan, Yang, Wen-Tao, Shi, Jin-Xiu, Huang, Wei, Hu, Xin, Shao, Zhi-Ming
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10-04-2018; Nature Publishing Group; Nature Portfolio
• Subjects: 1-Phosphatidylinositol 3-kinase; 45/47; 45/70; 631/67/1347; 631/67/69; Breast cancer; Cancer; Deregulation; Humanities and Social Sciences; Hyperactivity; multidisciplinary; Mutation; Patients; Precision medicine; PTEN protein; Recombination; Science; Science (multidisciplinary); Tumorigenesis; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-03867-9

Deregulation of the phosphoinositide 3-kinase (PI3K) pathway contributes to the development and progression of tumors. Here, we determine that somatic mutations in
PIK3CA
(44%),
PIK3R1
(17%),
AKT3
(15%), and
PTEN
(12%) are prevalent and diverse in Chinese breast cancer patients, with 60 novel mutations identified. A high proportion of tumors harbors multiple mutations, especially
PIK3CA
plus
PIK3R1
mutations (9.0%). Next, we develop a recombination-based mutation barcoding (ReMB) library for impactful mutations conferring clonal advantage in proliferation and drug responses. The highest-ranking
PIK3CA
and
PIK3R1
mutations include previously reported deleterious mutations, as well as mutations with unknown significance. These
PIK3CA
and
PIK3R1
impactful mutations exhibit a mutually exclusive pattern, leading to oncogenesis and hyperactivity of PI3K pathway. The
PIK3CA
impactful mutations are tightly associated with hormone receptor positivity. Collectively, these findings advance our understanding of PI3K impactful mutations in breast cancer and have important implications for PI3K-targeted therapy in precision oncology.
The PI3K pathway is altered across various cancer types. Here the authors use amplicon exon sequencing to analyze the landscape of somatic mutations affecting the PI3K pathway specifically in breast cancer patients in China.