Haplotype-specific assembly of shattered chromosomes in esophageal adenocarcinomas.

ABSTRACT: The epigenetic landscape of cancer is regulated by many factors, but primarily it derives from the underlying genome sequence. Chromothripsis is a catastrophic localized genome shattering event that drives, and often initiates, cancer evolution. We characterized five esophageal adenocarcinoma organoids with chromothripsis using long-read sequencing and transcriptome and epigenome profiling. Complex structural variation and subclonal variants meant that haplotype-aware de novo methods were required to generate contiguous cancer genome assemblies. Chromosomes were assembled separately and scaffolded using haplotype-resolved Hi-C reads, producing accurate assemblies even with up to 900 structural rearrangements. There were widespread differences between the chromothriptic and wild-type copies

SUBMITTER: Ijaz J 

PROVIDER: S-EPMC10879010 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature