A Germline Mutation in ATR Is Associated With Lung Adenocarcinoma in Asian Patients

Guangyao Bao; Xiaojiao Guan; Jie Liang; Yao Yao; Yifan Xiang; Tian Li; Xinwen Zhong

doi:10.3389/fonc.2022.855305

A Germline Mutation in ATR Is Associated With Lung Adenocarcinoma in Asian Patients

Front Oncol. 2022 May 31:12:855305. doi: 10.3389/fonc.2022.855305. eCollection 2022.

Authors

Guangyao Bao¹, Xiaojiao Guan², Jie Liang¹, Yao Yao¹, Yifan Xiang¹, Tian Li³, Xinwen Zhong¹

Affiliations

¹ Department of Thoracic Surgery, First Affiliated Hospital, China Medical University, Shenyang, China.
² Department of Pathology, Shengjing Hospital, China Medical University, Shenyang, China.
³ School of Basic Medicine, Fourth Military Medical University, Xi'an, China.

Abstract

Background: Familial lung cancer (FLC) accounts for 8% of lung adenocarcinoma. It is known that a few germline mutations are associated with risk increasing and may provide new screening and treatment option. The goal of this study is to identify an FLC gene among three members of an FLC family.

Methods: To uncover somatic and embryonic mutations linked with familial lung cancer, whole exome sequencing was done on surgical tissues and peripheral blood from three sisters in a family diagnosed with pulmonary lung adenocarcinoma (LUAD). At the same time, single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data in public databases were enrolled to identify specific gene expression level.

Results: Ataxia Telangiectasia and Rad3-Related Protein (ATR) gene C.7667C >G (p.T2556S) mutation were found in 3 patients with familial lung cancer. Whole-genome sequencing revealed that the three sisters exhibited similar somatic mutation patterns. Besides ATR mutations, common mutated genes (BRCA1, EGFR, and ROS1) that characterize LUAD were also found in 5 tumor samples. Analysis for the ATR expression in LUAD patients by single-cell sequencing data, we found ATR expression of tumor patients at high level in immune cells when compared with normal patients, but the expression of ATR in stromal cells has the opposite result.

Conclusion: We found a germline mutation in the ATR gene in three sisters of a Chinese family affected by familial lung cancer, which may be a genetic factor for lung cancer susceptibility.

Keywords: ATR; familiar lung cancer; germline mutation; lung adenocarcinoma; sequencing.