Germline Mutation of T790M and Dual/Multiple EGFR Mutations in Patients With Lung Adenocarcinoma.

Introduction: The epidermal growth factor receptor ( T790M mutation remains one of the major mechanisms of resistance to tyrosine kinase inhibitors (TKI) treatment. Cases of T790M mutations prior to TKI treatment have been reported, but most of them were somatic mutations. In this study, we report a case of primary dual mutations containing a germline T790M mutation in a NSCLC patient. We further describe a case series of NSCLC patients who had primary dual or multiple mutations.

Methods: mutation status was analyzed in 427 patients with lung adenocarcinomas. Clinical, demographic data and sequencing electropherograms were collected on patients with two or more mutations identified prior to TKI treatment. Peripheral blood mononuclear cells were sequenced for germ-line mutation on two patients with primary T790M mutation.

Results: 55 out of 427 (13%) patients with lung adenocarcinomas were found to have mutations; twelve of which were identified to have either dual or multiple mutations. Five of these 12 patients (42%) had primary T790M mutation and three of them showed similar heights of the mutant and wild-type peaks on sequencing electropherogram, suggesting the possibility of germline mutation. One case of germline T790M mutation was confirmed via sequencing a peripheral blood sample.

Conclusions: Dual or multiple mutations comprised 2.8% of lung adenocarcinomas in our study. Primary T790M mutation are presented with high frequency (5/12; 42%) in patients carrying dual or multiple mutations.