Yu Helena A, Arcila Maria E, Harlan Fleischut Megan, Stadler Zsofia, Ladanyi Marc, Berger Michael F, Robson Mark, Riely Gregory J
*Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine; †Department of Pathology, ‡Clinical Genetics Service, Department of Medicine, §Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York; and ‖Weill Cornell Medical College, New York, New York.
J Thorac Oncol. 2014 Apr;9(4):554-8. doi: 10.1097/JTO.0000000000000052.
Activating mutations in epidermal growth factor receptor (EGFR) are present in a subset of lung cancers, and predict sensitivity to EGFR tyrosine kinase inhibitors. Acquisition of EGFR T790M is the most common mechanism of resistance to EGFR tyrosine kinase inhibitors and rarely is seen before treatment. Germline EGFR T790M mutations have been reported, although the penetrance and clinical significance of this mutation is unknown. We describe the identification of a patient with an EGFR T790M germline mutation and subsequent germline testing in her unaffected family members. Genetic testing revealed two additional EGFR T790M germline carriers, one of which was subsequently diagnosed with metastatic lung adenocarcinoma.
表皮生长因子受体（EGFR）的激活突变存在于一部分肺癌中，并预示着对EGFR酪氨酸激酶抑制剂敏感。EGFR T790M的获得是对EGFR酪氨酸激酶抑制剂耐药的最常见机制，且在治疗前很少见。虽然该突变的外显率和临床意义尚不清楚，但已有胚系EGFR T790M突变的报道。我们描述了一名患有EGFR T790M胚系突变患者的鉴定以及随后对其未受影响家庭成员的胚系检测。基因检测发现另外两名EGFR T790M胚系携带者，其中一人随后被诊断为转移性肺腺癌。
