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

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Jun 17

PMID 35712480

Authors

Guangyao Bao

Xiaojiao Guan

Jie Liang

Yao Yao

Yifan Xiang

Tian Li

Xinwen Zhong

Affiliations

Soon will be listed here.

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.

Citing Articles

The mathematical exploration for the mechanism of lung adenocarcinoma formation and progression.

Han Y, Chen B, Bi Z, Bian J, Kang R, Shang X Brief Bioinform. 2024; 25(6).

PMID: 39562161 PMC: 11576079. DOI: 10.1093/bib/bbae603.

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