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Characterization of AKT Somatic Mutations in Chinese Breast Cancer Patients

Authors Wen L, Zhang G, Ren C, Li X, Mok H, Jia M, Wang Y, Chen B, Li K, Cao L, Li C, Xiao W, Lai J, Lin J, Wei G, Li Y, Zhang Y, Chen X, Liao N

Received 7 January 2021

Accepted for publication 17 March 2021

Published 7 April 2021 Volume 2021:13 Pages 3055—3065

DOI https://doi.org/10.2147/CMAR.S299624

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Lingzhu Wen,1,* Guochun Zhang,1,* Chongyang Ren,1,* Xuerui Li,1 Hsiaopei Mok,1 Minghan Jia,1 Yulei Wang,1 Bo Chen,1 Kai Li,1 Li Cao,1 Cheukfai Li,1 Weikai Xiao,1 Jianguo Lai,1 Jiali Lin,1 Guangnan Wei,1 Yingzi Li,1 Yuchen Zhang,1 Xiaoqing Chen,2 Ning Liao1

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

*These authors contributed equally to this work

Correspondence: Ning Liao
Department of Breast Cancer, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), No. 106, Zhongshan 2nd Road, Yuexiu District, Guangzhou, Guangdong, People’s Republic of China
Tel/Fax +86 20-83827812
Email [email protected]

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, next-generation sequencing, breast cancer, somatic mutations, population study

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