Ongoing genome doubling shapes evolvability and immunity in ovarian cancer.

ABSTRACT: Whole-genome doubling (WGD) is a common feature of human cancers and is linked to tumour progression, drug resistance, and metastasis^1-6. Here we examine the impact of WGD on somatic evolution and immune evasion at single-cell resolution in patient tumours. Using single-cell whole-genome sequencing, we analysed 70 high-grade serous ovarian cancer samples from 41 patients (30,260 tumour genomes) and observed near-ubiquitous evidence that WGD is an ongoing mutational process. WGD was associated with increased cell-cell diversity and higher rates of chromosomal missegregation and consequent micronucleation. We developed a mutation-based WGD timing method called doubleTime to delineate specific modes by which WGD can drive tumour evolution, including early fixation followed by consi

SUBMITTER: McPherson A 

PROVIDER: S-EPMC12390843 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature