Molecular Characteristics of EGFR Exon20 Mutations in NSCLC Patients.

e21011 Background: EGFR exon 20 mutations are associated with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). EGFR exon 20 mutations are usually not present alone, suggesting a more complex subtype of exon 20 mutations. Methods: In this study, we retrospectively analyzed the different subtypes and compound mutation profiles of EGFR 20 mutations. A total of 1,233 NSCLC patients’ tumors were collected and the mutations were detected by next-generation sequencing (NGS) from May 2020 to June 2021. Results: A total of 415 NSCLC patients' tumors harbored EGFR exon 20 mutations, accounting for 33.66% of the entire EGFR mutation cohort. Among these 415 patients, most of mutations were single-nucleotide variant (SNV) (379; 91.33%), and a few were indel or insertion mutations (39; 9.40%). The insertions were all in the back of exon 20, which were resistant to EGFR-TKIs. In addition, the subtypes of SNV were concentrated in T790M (270; 71.24%), S768I (48; 12.66%) and C797S (33; 8.71%), and all T790M mutations were accompanied by other mutations. Notably, the compound mutations of exon 20 have also been analyzed in this study. EGFR exon 20 combined with other EGFR mutations were detected in 345 patients. The compound mutations of exon 20-18, exon 20-19, exon 20-20 and exon 20-21 were detected in tumors from 52 (15.07%), 163 (47.25%), 43 (12.46%) and 140 (40.58%) patients respectively. Remarkably, the compound mutation subtype of exon 20-20 was T790M/C797X (29; 67.55%) and exon 20-21 was T790M/L858R (124; 88.57%). Conclusions: Diverse patterns of SNV mutations are seen in EGFR exon 20 mutations tumors. EGFR 20 mutations often accompany other mutations, which are associated with resistance to EGFR-TKIs. These data may help avoid the resistance of future adjuvant targeted therapy.