Characterization of AKT Somatic Mutations in Chinese Breast Cancer Patients

Lingzhu Wen; Guochun Zhang; Chongyang Ren; Xuerui Li; Hsiaopei Mok; Minghan Jia; Yulei Wang; Bo Chen; Kai Li; Li Cao; Cheukfai Li; Weikai Xiao; Jianguo Lai; Jiali Lin; Guangnan Wei; Yingzi Li; Yuchen Zhang; Xiaoqing Chen; Ning Liao

doi:10.2147/CMAR.S299624

Characterization of AKT Somatic Mutations in Chinese Breast Cancer Patients

Cancer Manag Res. 2021 Apr 7:13:3055-3065. doi: 10.2147/CMAR.S299624. eCollection 2021.

Authors

Lingzhu Wen^#¹, Guochun Zhang^#¹, Chongyang Ren^#¹, Xuerui Li¹, Hsiaopei Mok¹, Minghan Jia¹, Yulei Wang¹, Bo Chen¹, Kai Li¹, Li Cao¹, Cheukfai Li¹, Weikai Xiao¹, Jianguo Lai¹, Jiali Lin¹, Guangnan Wei¹, Yingzi Li¹, Yuchen Zhang¹, Xiaoqing Chen², Ning Liao¹

Affiliations

¹ Department of Breast Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Guangzhou, Guangdong, People's Republic of China.
² Department of Breast Surgical Oncology, Foshan Maternity and Children's Healthcare Hospital Affiliated to Southern Medical University, Foshan, Guangdong, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: This study aimed to investigate AKT gene mutation status in Chinese breast cancer patients.

Methods: The study included 411 breast cancer patients hospitalized in Guangdong Provincial People's Hospital (GDPH) from June 1, 2017 to September 27, 2018. Mastectomy or breast conserving surgery was performed, and tissue samples were subjected to next-generation sequencing (NGS) to determine AKT gene mutation status. Meanwhile, the expression of human epidermal growth factor receptor 2 (Her2), progesterone receptor (PR), and estrogen receptor (ER) was analyzed by immunohistochemistry staining. The Cancer Genome Atlas (TCGA) database was used for comparative studies.

Results: Patients in the GDPH cohort had an older age (P < 0.001), higher postmenopausal rate (P < 0.001), larger tumor size (P < 0.001), higher histologic type of infiltrating duct cancer (P < 0.001), higher metastatic rate (P < 0.001), higher expression of ER (P = 0.015) and HER2 (P < 0.001), and higher percentage of the HR/HER2 subtype (P < 0.001) than those in the TCGA cohort. The GDPH cohort displayed lower rates of overall AKT and AKT3 mutation (P < 0.001), but a higher AKT1 mutation rate (P < 0.0001) compared with the TCGA cohort. Notably, the NGS studies identified missense mutation and copy number amplification as the most common AKT variation type in the GDPH and TCGA cohorts, respectively. Specifically, E17K mutation in AKT1 was predominantly detected in GDPH cohort, while being absent in TCGA cohort. Moreover, in the GDPH cohort, AKT variation was correlated with a number of clinicopathological variables, including age over 50, HER2-, HR+/HER2-, and PR+.

Conclusion: Patients in the GDPH cohort had lower rates of AKT and AKT3 mutation and higher AKT1 mutation rate than those in the TCGA cohort, while harboring missense mutations detected predominantly as E17K mutation in AKT1. In GDPH cohort, there were correlations between AKT mutation and the clinicopathological characteristics of patients.

Keywords: AKT; breast cancer; next-generation sequencing; population study; somatic mutations.

Grants and funding

This work was supported by funds from High-level Hospital Construction Project (DFJH201921, Bo Chen); the National Natural Science Foundation of China (81902828, Bo Chen; 82002928, Jianguo Lai); Natural Science Foundation of Guangdong Province (2016A030313768, Ning Liao; 2018A030313292) and Research Funds from Guangzhou Municipal Science and Technology Project (201707010418, Ning Liao); the Fundamental Research Funds for the Central Universities (y2syD2192230, Bo Chen); Medical Scientific Research Foundation of Guangdong Province (B2019039, Bo Chen); the Doctor Launch Fund of Guangdong Provincial People’s hospital (2018bq02,Bo Chen; 2020bq11, Jianguo Lai) and Research Funds from Guangzhou Municipal Science and Technology Project (grant numbers: 201707010418; 201804010430). The funding bodies have no role in the design of the study, the collection, analysis, and interpretation of data and in writing the manuscript.