Germline mutations and developmental mosaicism underlying <i>EGFR</i>-mutant lung cancer.

ABSTRACT: While the development of multiple primary tumors in smokers with lung cancer can be attributed to carcinogen-induced field cancerization, the occurrence of multiple primary tumors in individuals with EGFR-mutant lung cancer who lack known environmental exposures remains unexplained. We identified ten patients with early-stage, resectable non-small cell lung cancer who presented with multiple anatomically distinct EGFR-mutant tumors. We analyzed the phylogenetic relationships among multiple tumors from each patient using whole exome sequencing (WES) and hypermutable poly-guanine (poly-G) repeat genotyping, as orthogonal methods for lineage tracing. In two patients, we identified germline EGFR variants, which confer moderately enhanced signaling when modeled in vitro<

SUBMITTER: Burr R 

PROVIDER: S-EPMC10557804 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature