DNA methylation cooperates with genomic alterations during non-small cell lung cancer evolution.

ABSTRACT: Aberrant DNA methylation has been described in nearly all human cancers, yet its interplay with genomic alterations during tumor evolution is poorly understood. To explore this, we performed reduced representation bisulfite sequencing on 217 tumor and matched normal regions from 59 patients with non-small cell lung cancer from the TRACERx study to deconvolve tumor methylation. We developed two metrics for integrative evolutionary analysis with DNA and RNA sequencing data. Intratumoral methylation distance quantifies intratumor DNA methylation heterogeneity. M_R/M_N classifies genes based on the rate of hypermethylation at regulatory (M_R) versus nonregulatory (M_N) CpGs to identify driver genes exhibiting recurrent functional hypermethylation. We ide

SUBMITTER: Gimeno-Valiente F 

PROVIDER: S-EPMC12425823 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature