Somatic whole genome dynamics of precancer in Barrett's esophagus reveals features associated with disease progression.

ABSTRACT: While the genomes of normal tissues undergo dynamic changes over time, little is understood about the temporal-spatial dynamics of genomes in premalignant tissues that progress to cancer compared to those that remain cancer-free. Here we use whole genome sequencing to contrast genomic alterations in 427 longitudinal samples from 40 patients with stable Barrett's esophagus compared to 40 Barrett's patients who progressed to esophageal adenocarcinoma (ESAD). We show the same somatic mutational processes are active in Barrett's tissue regardless of outcome, with high levels of mutation, ESAD gene and focal chromosomal alterations, and similar mutational signatures. The critical distinction between stable Barrett's versus those who progress to cancer is acquisition and expansion of TP53-/- cel

SUBMITTER: Paulson TG 

PROVIDER: S-EPMC9050715 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature