中国西南地区肺癌患者基因突变特点及其与临床特征的相关性分析

Characteristics of Gene Mutations in Lung Cancer Patients in Southwest China and Analysis of Their Correlation with Clinical Features

摘要: 目的：探究中国西南地区肺癌患者肿瘤易感基因胚系突变与体细胞突变特点及其临床病理特征。方法：回顾性分析重庆医科大学附属第一医院2019年1月至2022年12月收治的1198例肺癌患者的胚系基因测序数据，根据美国医学遗传学与基因组学学会遗传突变分类标准指南、Clinvar数据库和Intervar数据库评估突变的致病性。比较携带基因致病性或可能致病性胚系突变(pathogenic/likely pathogenic, P/LP)患者与未携带基因致病性或可能致病性胚系突变患者的临床病理特征及体细胞突变特点。结果：1198例肺癌患者中，108例(9.02%)患者纳入P/LP+组，其中BRCA2基因突变10例，ATM基因突变8例，NOTCH3基因突变6例，FANCM基因突变5例，有56例患者伴发有EGFR体细胞突变，5例患者伴发有ALK体细胞突变；1090例(90.98%)患者纳入P/LP−组。与P/LP−组比较，P/LP+组患者临床分期多处于晚期(P < 0.05)，而在年龄、性别、吸烟史、饮酒史、既往肿瘤史、多原发肿瘤史、家族肿瘤史方面未发现明显的差异(均 P > 0.05)。P/LP+组与P/LP−组在体细胞突变上差异无统计学意义(P > 0.05)。结论：中国西南地区肺癌患者中致病性或可能致病性胚系突变发生率约为9%，携带有P/LP胚系突变的患者临床分期多为晚期，肺癌中P/LP胚系突变与驱动基因突变间未发现相关性。

Abstract: Objective: To examine the characteristics of germline and somatic mutations in tumor susceptibility genes among lung cancer patients in Southwest China, and to analyze their associations with clinicopathological features. Methods: This retrospective study analyzed germline gene sequencing data from 1198 lung cancer patients treated at The First Affiliated Hospital of Chongqing Medical University between January 2019 and December 2022. The pathogenicity of mutations was assessed according to the guidelines of the American College of Medical Genetics and Genomics (ACMG), as well as data from the Clinvar and Intervar databases. Clinicopathological characteristics and somatic mutation profiles were compared between patients with pathogenic or likely pathogenic germline mutations (P/LP group) and those without such mutations (non-P/LP group). Results: Of the 1198 lung cancer patients, 108 (9.02%) were classified into the P/LP+ group, with mutations identified in BRCA2 (10 cases), ATM (8 cases), NOTCH3 (6 cases), and FANCM (5 cases). Additionally, 56 patients in the P/LP+ group harbored concurrent EGFR somatic mutations, and 5 had concurrent ALK somatic mutations. The remaining 1090 patients (90.98%) were categorized into the non-P/LP− group. Compared with the non-P/LP− group, patients in the P/LP+ group were more likely to be diagnosed at an advanced clinical stage (P < 0.05). However, no significant differences were observed between the two groups regarding age, sex, smoking history, alcohol consumption, prior cancer history, multiple primary tumor history, or family history of cancer (all P > 0.05). Somatic mutation profiles did not differ significantly between the P/LP+ and non-P/LP− groups (P > 0.05). Conclusion: The prevalence of pathogenic or likely pathogenic germline mutations in lung cancer patients in Southwest China is approximately 9%. Patients with P/LP germline mutations are more likely to present at advanced stages. No significant correlation was observed between P/LP germline mutations and driver gene mutations in lung cancer.