Lin Xinqing, Peng Muyun, Chen Quanfang, Yuan Mingming, Chen Rongrong, Deng Haiyi, Deng Jiaxi, Liu Ouqi, Weng Yuqing, Chen Mingjiu, Zhou Chengzhi
State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Department of Thoracic Surgery, Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, The Second Xiangya Hospital of Central South University, Changsha, China.
Front Oncol. 2021 Nov 16;11:774156. doi: 10.3389/fonc.2021.774156. eCollection 2021.
Epidemiological surveys have suggested that lung cancer has inherited susceptibility and shows familial aggregation. However, the distribution and prevalence of epidermal growth factor receptor () germline variants and their roles in lung cancer genetic predisposition in Chinese population remain to be elucidated.
In this study, germline and somatic variants were retrospectively reviewed from the next-generation sequencing results of 31,906 patients with lung cancer. Clinical information was also collected for patients with confirmed EGFR germline mutations.
A total of 22 germline variants were identified in 64 patients with lung cancer, accounting for 0.2% of the total cases studied. Five patients were diagnosed as multiple primary carcinomas. Family history was documented in 31.3% (20/64) of patients, 55% of which were diagnosed as lung cancer. G863D was the most frequent germline mutation, followed by P848L, D1014N, and K757R. Somatic -sensitive mutations were identified in 51.6% of patients with germline mutations. The proportion of L858R mutation, exon 19 deletion, and rare sensitive mutation was 50%, 17.6%, and 32.4%, respectively. D1014N and T790M mutations were common in young patients. The family members of patients with P848L, R776H, V769M, and V774M mutations were more commonly diagnosed with cancers. A total of 19 patients were confirmed to have received EGFR tyrosine kinase inhibitors (TKIs), but the response to EGFR-TKIs differed among patients with different mutations.
Chinese patients with lung cancer harbored unique and dispersive germline mutations and showed unique clinical and genetic characteristics, with varied response patterns to EGFR-TKI treatment.
流行病学调查表明肺癌存在遗传易感性并呈现家族聚集性。然而，表皮生长因子受体（EGFR）种系变异在中国人群中的分布、患病率及其在肺癌遗传易感性中的作用仍有待阐明。
在本研究中，对31906例肺癌患者的二代测序结果进行回顾性分析，以检测种系和体细胞变异。同时收集确诊为EGFR种系突变患者的临床信息。
在64例肺癌患者中总共鉴定出22种EGFR种系变异，占所研究病例总数的0.2%。5例患者被诊断为多原发性癌。31.3%（20/64）的患者有家族史，其中55%被诊断为肺癌。G863D是最常见的EGFR种系突变，其次是P848L、D1014N和K757R。51.6%的种系EGFR突变患者中检测到体细胞EGFR敏感突变。L858R突变、外显子19缺失和罕见敏感突变的比例分别为50%、17.6%和32.4%。D1014N和T790M突变在年轻患者中常见。P848L、R776H、V769M和V774M突变患者的家庭成员更常被诊断为癌症。共有19例患者被证实接受过EGFR酪氨酸激酶抑制剂（TKIs）治疗，但不同EGFR突变患者对EGFR-TKIs的反应不同。
中国肺癌患者存在独特且分散的EGFR种系突变，并表现出独特的临床和遗传特征，对EGFR-TKI治疗有不同的反应模式。
