Li Yingxue, Li Guangqi, Zheng Zheng, Wen Wenjuan, Zhao Haihui, Liu Xia, Xie Jiaping, Han Lin
Department of Pathology, Liaocheng People's Hospital, Liaocheng, 252000, Shandong, People's Republic of China.
Department of Pathology, School of Basic Medicine Science, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
Hered Cancer Clin Pract. 2024 Aug 19;22(1):13. doi: 10.1186/s13053-024-00286-4.
Somatic mutations in the EGFR gene occur in about 50% of non-small cell lung cancers, with the T790M mutation significantly contributing to secondary resistance against EGFR-TKI drugs. However, EGFR T790M germline mutations rarely occur.
In this study, we report a case of a lung adenocarcinoma family lineage linked to a germline EGFR T790M mutation. The main subject was diagnosed with stage IV lung adenocarcinoma and experienced a 19-month period without disease progression while treated with Osimertinib. We collected both clinicopathological and familial data from a patient with lung adenocarcinoma. Next-generation sequencing of 40 key genes was performed on the proband's tumor tissue. To detect EGFR germline mutations, Sanger sequencing was conducted on peripheral blood mononuclear cells from the proband and his two daughters. Mutations such as EGFR T790M, EGFR 19-Del, TP53, and PIK3CA were identified in the proband's lung cancer tissue. Additionally, germline EGFR T790M mutations were confirmed in the proband and his daughters through sequencing of their peripheral blood samples. CT scans revealed multiple pulmonary nodules in both daughters.
These observations suggest that germline mutations in EGFR T790M could be strongly linked to a familial predisposition to lung cancer.
表皮生长因子受体（EGFR）基因的体细胞突变约发生于50%的非小细胞肺癌中，其中T790M突变是导致对EGFR酪氨酸激酶抑制剂（EGFR-TKI）药物产生继发性耐药的重要原因。然而，EGFR T790M种系突变很少发生。
在本研究中，我们报告了一例与种系EGFR T790M突变相关的肺腺癌家族谱系病例。主要患者被诊断为IV期肺腺癌，在接受奥希替尼治疗期间有19个月无疾病进展。我们收集了一名肺腺癌患者的临床病理和家族数据。对先证者的肿瘤组织进行了40个关键基因的二代测序。为检测EGFR种系突变，对先证者及其两个女儿的外周血单个核细胞进行了桑格测序。在先证者的肺癌组织中发现了EGFR T790M、EGFR 19号外显子缺失、TP53和PIK3CA等突变。此外，通过对他们外周血样本的测序，在先证者及其女儿中证实了种系EGFR T790M突变。CT扫描显示两个女儿均有多个肺结节。
这些观察结果表明，EGFR T790M种系突变可能与肺癌的家族易感性密切相关。
