Co-occurring genetic alterations and primary EGFR T790M mutations detected by next-generation sequencing in pre-TKI treated patients with non-small cell lung cancer.

Abstract

e13128 Background: With the development of targeted drugs, there are more therapeutic options for patients with non-small cell lung cancer (NSCLC) harboring corresponding genetic alterations. However, cancers are frequently caused by alterations on multiple genes, which collaborate to promote tumor development. Methods: A total of 1353 NSCLC patients from five different clinical institutions were enrolled in this study. Concurrent DNA and RNA NGS analysis was performed using the Ion Ampliseq Colon and Lung Cancer gene panel v2 and the AmpliSeq RNA Lung Cancer Research Fusion Panel using FFPE samples from surgically resected NSCLC tumors. Results: Of the 1293 mutations that were detected, 2338 variants were identified in 24 genes, while 27 of the tumor samples were identified to have co-occurring DNA mutations (including insertions, deletions and point mutations) and RNA fusion mutations. Analysis of the 975 patients with EGFR-gene mutations revealed that the incidence of dual EGFR L858R/T790M mutations were higher compared to EGFR 19del/T790M, and the MAF of T790M was lower compared to 19del in dual EGFR 19del/T790M patients. Conclusions: Even with the non-random cohort of patients in this study, the genetic alterations detected in this study had a certain degree of representation of NSCLC (especially lung adenocarcinoma) in the Chinese population. The differences in the MAF of EGFR T790M may determine different responses to TKI therapy in patients harboring dual mutations.