Methylation Signatures Associated With T790m Status In Progressive Nsclc

Background: Emergence of the EGFR T790M mutation accounts for acquired first generation EGFR TKI resistance in over half of patients with EGFR mutant NSCLC. In patients without emergent T790M, resistance mechanisms are less well understood. We explored the impact of DNA methylation status and TKI treatment failure in these patients. Methods: Using a prospective cohort of patients with acquired TKI resistance, tumour tissue samples pre/post TKI exposure were identified. DNA was extracted from FFPE tissue using the Qiagen AllPrep DNA/RNA FFPE Extraction Protocol, and subsequently analyzed using the Illumina Infinium EPIC array. Raw microarray data files were processed using the software package minfi for data normalization (Illumina method) and extraction of methylation levels (M-values). Samples were split into two groups according to the T790M status of each sample (T790M + or T790M …