Identification of Germline Mutations in East‑Asian Young Never‑Smokers with Lung Adenocarcinoma by Whole‑Exome Sequencing  

作　　者：Fangqiu Fu Xiaoting Tao Zhonglin Jiang Zhendong Gao Yue Zhao Yuan Li Hong Hu Libing Shen Yihua Sun Yang Zhang 

机构地区：[1]Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering,Fudan University Shanghai Cancer Center,270 Dong‑An Road,Shanghai 200032,China [2]Institute of Thoracic Oncology,Fudan University,Shanghai 200032,China [3]Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China [4]Key Laboratory of Systems Biology,Center for Excellence in Molecular Cell Science,Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,University of Chinese Academy of Sciences,Shanghai 200031,China [5]Department of Pathology,Fudan University Shanghai Cancer Center,Shanghai 200032,China [6]International Human Phenome Institutes(Shanghai),Shanghai 200433,China

出　　处：《Phenomics》2023年第2期182-189,共8页表型组学（英文）

基　　金：supported by the National Natural Science Foundation of China(81772466);Shanghai Rising-Star Program(21QC1400600);Ministry of Science and Technology of the People’s Republic of China(2017YFA0505500,2016YFA0501800);Science and Technology Commission of Shanghai Municipality(19XD1401300).

摘　　要：Recently,an increasing number of young never-smokers are diagnosed with lung cancer.The aim of this study is to investigate the genetic predisposition of lung cancer in these patients and discover candidate pathogenic variants for lung adenocarcinoma in young never-smokers.Peripheral blood was collected from 123 never-smoking east-Asian patients diagnosed with lung adenocarcinoma before the age of 40.Whole-exome sequencing(WES)was conducted on genomic DNA extracted from peripheral blood cells.As a result,3,481 single nucleotide variants were identified.By bioinformatical tools and the published gene list associated with genetic predisposition of cancer,pathogenic variants were detected in ten germline genes:ATR,FANCD2,FANCE,GATA2,HFE,MSH2,PDGFRA,PMS2,SDHB,and WAS.Patients with pathogenic variants were more likely to occur in females(9/10,90.0%)and have stage IV lung adenocarcinoma(4/10,40%).Furthermore,germline muta-tions in 17 genes(ASB18,B3GALT5,CLEC4F,COL6A6,CYP4B1,C6orf132,EXO1,GATA4,HCK,KCP,NPHP4,PIGX,PPIL2,PPP1R3G,RRBP1,SALL4,and TTC28),which occurred in at least two patients,displayed potentially pathogenic effects.Gene ontology analysis further showed that these genes with germline mutations were mainly located in nucleo-plasm and associated with DNA repair-related biological processes.The study provides spectrum of pathogenic variants and functional explanation for genetic predisposition of lung adenocarcinoma in young never-smokers,which sheds a light on prevention and early diagnosis of lung cancer.

关 键 词：Lung adenocarcinoma Germline mutation Never-smoker Young age DNA repair 

分 类 号：R734.2[医药卫生—肿瘤]