The co-evolution of the genome and epigenome in colorectal cancer.

ABSTRACT: Colorectal malignancies are a leading cause of cancer-related death¹ and have undergone extensive genomic study^2,3. However, DNA mutations alone do not fully explain malignant transformation^4-7. Here we investigate the co-evolution of the genome and epigenome of colorectal tumours at single-clone resolution using spatial multi-omic profiling of individual glands. We collected 1,370 samples from 30 primary cancers and 8 concomitant adenomas and generated 1,207 chromatin accessibility profiles, 527 whole genomes and 297 whole transcriptomes. We found positive selection for DNA mutations in chromatin modifier genes and recurrent somatic chromatin accessibility alterations, including in regulatory regions of cancer driver genes that were otherwise devoid of gen

SUBMITTER: Heide T 

PROVIDER: S-EPMC9684080 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature