Evolutionary characterization of whole-genome doubling across human cancers
Abstract
Whole-genome doubling (WGD) is common across human cancers and is associated with tumour progression and adverse clinical outcomes. However, how genome-doubled tumours evolve across diverse cancer types remains poorly understood. Here we characterize WGD-associated tumour evolution by integrating genomic analyses of 41,332 tumours from 12 cancer types with evolutionary timing and multi-omic data. Several canonical driver mutations generally preceded WGD when both occurred, as did the onset of homologous recombination deficiency-associated mutagenesis. Notably, post-WGD chromosome-arm losses showed substantially weaker cancer-type dependence than pre-WGD losses, with 61-75% less variance explained by cancer type. Beyond chromosomal evolution, WGD+ tumours showed reduced interferon-response and HLA antigen-presentation programmes linked to epigenetic remodelling, without disproportionate enrichment of genetic immune-escape alterations. Our findings highlight WGD as a recurrent evolutionary transition associated with altered chromosomal evolution and epigenetically linked immune adaptation across cancers.
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BibTeX
@misc{zhang2026evolutionary,
title = {{Evolutionary characterization of whole-genome doubling across human cancers}},
author = {Yangyang Zhang and Haiming Li and Xiaoyu Zhao and Zilong Wang and Yongqi Chen and Sumeng Yang and Shaocong Mo and Jinming Li and Xiaohua Wu and Xu Wang and Shuo Wang and Qinhao Guo},
howpublished = {arXiv},
year = {2026},
month = nov,
doi = {10.48550/arxiv.2611.01897},
eprint = {2611.01897},
archivePrefix = {arXiv},
url = {https://arxiv.org/abs/2611.01897},
}
RIS
TY - UNPB
TI - Evolutionary characterization of whole-genome doubling across human cancers
AU - Yangyang Zhang
AU - Haiming Li
AU - Xiaoyu Zhao
AU - Zilong Wang
AU - Yongqi Chen
AU - Sumeng Yang
AU - Shaocong Mo
AU - Jinming Li
AU - Xiaohua Wu
AU - Xu Wang
AU - Shuo Wang
AU - Qinhao Guo
PY - 2026
DA - 2026/11/01
PB - arXiv
DO - 10.48550/arxiv.2611.01897
UR - https://arxiv.org/abs/2611.01897
AB - Whole-genome doubling (WGD) is common across human cancers and is associated with tumour progression and adverse clinical outcomes. However, how genome-doubled tumours evolve across diverse cancer types remains poorly understood. Here we characterize WGD-associated tumour evolution by integrating genomic analyses of 41,332 tumours from 12 cancer types with evolutionary timing and multi-omic data. Several canonical driver mutations generally preceded WGD when both occurred, as did the onset of homologous recombination deficiency-associated mutagenesis. Notably, post-WGD chromosome-arm losses showed substantially weaker cancer-type dependence than pre-WGD losses, with 61-75% less variance explained by cancer type. Beyond chromosomal evolution, WGD+ tumours showed reduced interferon-response and HLA antigen-presentation programmes linked to epigenetic remodelling, without disproportionate enrichment of genetic immune-escape alterations. Our findings highlight WGD as a recurrent evolutionary transition associated with altered chromosomal evolution and epigenetically linked immune adaptation across cancers.
ER -