Germline Mutations in DNA Repair Genes in Lung Adenocarcinoma.
Germline Mutations in DNA Repair Genes in Lung Adenocarcinoma.
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DOI：
10.1016/j.jtho.2017.08.011
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Armanios M
中科院分区：
文献类型：
--
作者：
Parry EM;Gable DL;Stanley SE;Khalil SE;Antonescu V;Florea L;Armanios M
虽然肺癌通常被认为是由环境引起的，但有报道称，可能存在遗传易感性因素。我们系统地检测了8个候选基因的生殖系突变是否可能是肺腺癌的危险因素。我们研究了作为癌症基因组图谱（TCGA）项目的一部分而生成生殖系序列数据的肺腺癌病例，但这些数据以前没有进行过分析。我们选择了八个基因，ATM，BRCA 2，CHEK 2，EGFR，PARK 2，TERT，TP 53和YAP 1，基于先前与肺癌的轶事关联或全基因组关联研究。在555例肺腺癌病例中，我们在5个基因中检测到14个致病性突变;它们的发生频率为2.5%，比值比为66（95置信区间，33至125，P<0.0001，卡方检验）。这些突变在ATM中最常见（50%），其次是TP 53，BRCA 2，EGFR和PARK 2。这些变异中的大多数（86%）已在其他家族性癌症综合征中报告。另外12例（2%）携带超罕见变异，这些变异被三种蛋白质预测程序预测为有害的;这些最常见的涉及ATM和BRCA 2。至少2.5%至4.5%的肺腺癌患者携带与孟德尔综合征癌症风险相关的生殖系变异。这些基因最常出现在DNA修复途径中。我们的数据表明，肺腺癌，类似于其他实体瘤，包含一个子集的患者具有遗传易感性。
While lung cancer is generally thought to be environmentally provoked, anecdotal familial clustering has been reported suggesting there may be genetic susceptibility factors. We systematically tested whether germline mutations in eight candidate genes may be risk factors for lung adenocarcinoma. We studied lung adenocarcinoma cases for whom germline sequence data had been generated as part of The Cancer Genome Atlas (TCGA) project, but that had not been previously analyzed. We selected eight genes, ATM, BRCA2, CHEK2, EGFR, PARK2, TERT, TP53, and YAP1, based on prior anecdotal association with lung cancer or genome wide association studies. Among 555 lung adenocarcinoma cases, we detected 14 pathogenic mutations in five genes; they occurred at a frequency of 2.5% and represented an odds ratio of 66 (95 confidence interval, 33 to 125, P<0.0001, chi-square test). The mutations fell most commonly in ATM (50%), followed by TP53, BRCA2, EGFR and PARK2. The majority (86%) of these variants had been reported in other familial cancer syndromes. Another 12 cases (2%) carried ultra-rare variants that were predicted to be deleterious by three protein prediction programs; these most frequently involved ATM and BRCA2. A subset of lung adenocarcinoma patients, at least 2.5% to 4.5%, carries germline variants that have been linked to cancer risk in Mendelian syndromes. The genes fall most frequently in DNA repair pathways. Our data indicate that lung adenocarcinoma, similar to other solid tumors, contains a subset of patients with inherited susceptibility.
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影响因子：
30.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Bell, DW;Gore, I;Haber, DA
通讯作者：
Haber, DA
影响因子：
120.7
作者：
Yang, Da;Khan, Sofia;Sun, Yan;Hess, Kenneth;Shmulevich, Ilya;Sood, Anil K.;Zhang, Wei
通讯作者：
Zhang, Wei
DOI：
10.1097/jto.0000000000000130
发表时间：
2014-04
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Gazdar A;Robinson L;Oliver D;Xing C;Travis WD;Soh J;Toyooka S;Watumull L;Xie Y;Kernstine K;Schiller JH
通讯作者：
Schiller JH
影响因子：
64.8
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network