Inactivating mutations and hypermethylation of the <i>NKX2‐1/TTF‐1</i> gene in non‐terminal respiratory unit‐type lung adenocarcinomas

Summary

The major driver mutations of lung cancer, EGFR mutations and EML 4‐ ALK fusion, are mainly detected in terminal respiratory unit ( TRU )‐type lung adenocarcinomas, which typically show lepidic and/or papillary patterns, but are rarely associated with a solid or invasive mucinous morphology. In order to elucidate the key genetic events in non‐ TRU ‐type lung cancer, we carried out whole‐exome sequencing on 43 non‐ TRU ‐type lung adenocarcinomas based on morphology (17 acinar, nine solid, and two enteric adenocarcinomas, and 15 adenocarcinomas with a mucinous morphology). Our analysis identified mutations in TP 53 (16/43, 37.2%), KRAS (13/43, 30.2%), and NKX 2‐1/ TTF ‐1 (7/43; 16.3%) as the top three significantly mutated genes, while the EGFR mutation was rare (1/43, 2.3%) in this cohort.