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

IF 3.7 Q2 GENETICS & HEREDITY Phenomics (Cham, Switzerland) Pub Date : 2022-06-11 eCollection Date: 2023-04-01 DOI:10.1007/s43657-022-00062-1
Fangqiu Fu, Xiaoting Tao, Zhonglin Jiang, Zhendong Gao, Yue Zhao, Yuan Li, Hong Hu, Libing Shen, Yihua Sun, Yang Zhang
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Abstract

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 mutations 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 nucleoplasm 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.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-022-00062-1.

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用全外显子测序鉴定东亚从不吸烟青年肺腺癌的种系突变。
最近,越来越多的从不吸烟的年轻人被诊断出患有癌症。本研究的目的是调查这些患者患癌症的遗传易感性,并发现年轻吸烟者肺腺癌的候选致病性变异。采集了123名从不吸烟的东亚患者的外周血,这些患者在40岁前被诊断为肺腺癌。对从外周血细胞中提取的基因组DNA进行全外显子组测序(WES)。结果,鉴定出3481个单核苷酸变体。通过生物信息学工具和已发表的与癌症遗传易感性相关的基因列表,在10个种系基因中检测到致病性变体:ATR、FANCD2、FANCE、GATA2、HFE、MSH2、PDGFRA、PMS2、SDHB和WAS。具有致病性变异的患者更有可能发生在女性(9/10,90.0%)和IV期肺腺癌(4/10,40%)。此外,在至少两名患者中发生的17个基因(ASB18、B3GALT5、CLEC4F、COL6A6、CYP4B1、C6orf132、EXO1、GATA4、HCK、KCP、NPHP4、PIGX、PPIL2、PPP1R3G、RRBP1、SALL4和TTC28)的种系突变显示出潜在的致病作用。基因本体论分析进一步表明,这些具有种系突变的基因主要位于核质中,并与DNA修复相关的生物学过程有关。该研究提供了年轻吸烟者肺腺癌遗传易感性的致病变异谱和功能解释,为癌症的预防和早期诊断提供了依据。补充信息:在线版本包含补充材料,可访问10.1007/s43657-022-00062-1。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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