Common cancer-driver mutations and their association with abnormally methylated genes in lung adenocarcinoma from never-smokers.

摘要: Abstract Objectives Lung adenocarcinoma in never-smokers accounts for 15–20% of all lung cancer. Although targetable mutations are more prevalent these tumors, the biological and clinical importance coexisting and/or mutually exclusive abnormalities is just emerging. This study evaluates relationships between common genetic epigenetic aberrations tumors. Materials methods Next-generation sequencing was employed to screen 20 commonly mutated cancer-driver genes 112 adenocarcinomas from never-smokers. The relationship with cancer-related methylation 59 genes, geographical/ethnic differences prevalence compared multiple East Asian never-smoker cohorts studied. Results most driver mutation detected 40% (45/112) tumors EGFR, followed by TP53 (18%), SETD2 (11%), SMARCA4 (11%). Over 72% (81/112) cases have at least one gene. While 30% (34/112) co-mutations two or 42% (47/112) only gene mutation. Differences some were seen versus US (mainly Caucasian) including a significantly lower rate EGFR among patients. Interestingly, aberrant associated wildtype Among 15 differentially methylated mutation, 14 mutant These findings independently validated using publicly available data. Conclusion Most harbor mutation/co-mutations. In absence that drives appear develop acquiring promoter silences tumor-suppressor genes.