Allele-specific activation, enzyme kinetics, and inhibitor sensitivities of EGFR exon 19 deletion mutations in lung cancer.

ABSTRACT: Oncogenic mutations within the epidermal growth factor receptor (EGFR) are found in 15 to 30% of all non-small-cell lung carcinomas. The term exon 19 deletion (ex19del) is collectively used to refer to more than 20 distinct genomic alterations within exon 19 that comprise the most common EGFR mutation subtype in lung cancer. Despite this heterogeneity, clinical treatment decisions are made irrespective of which EGFR ex19del variant is present within the tumor, and there is a paucity of information regarding how individual ex19del variants influence protein structure and function. Herein, we identified allele-specific functional differences among ex19del variants attributable to recurring sequence and structure motifs. We built all-atom structural models of 60 ex19del variants identified in

SUBMITTER: Brown BP 

PROVIDER: S-EPMC9335329 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature