Please use this identifier to cite or link to this item:
https://hdl.handle.net/2445/205762
Title: | Cell cycle gene alterations associate with a redistribution of mutation risk across chromosomal domains in human cancers |
Author: | Salvadores Ferreiro, Marina Supek, Fran |
Keywords: | Heterocromatina Mutació (Biologia) Heterochromatin Mutation (Biology) |
Issue Date: | 10-Jan-2024 |
Publisher: | Springer Nature |
Abstract: | Mutations in human cells exhibit increased burden in heterochromatic, late DNA replication time (RT) chromosomal domains, with variation in mutation rates between tissues mirroring variation in heterochromatin and RT. We observed that regional mutation risk further varies between individual tumors in a manner independent of cell type, identifying three signatures of domain-scale mutagenesis in >4,000 tumor genomes. The major signature reflects remodeling of heterochromatin and of the RT program domains seen across tumors, tissues and cultured cells, and is robustly linked with higher expression of cell proliferation genes. Regional mutagenesis is associated with loss of activity of the tumor-suppressor genes RB1 and TP53, consistent with their roles in cell cycle control, with distinct mutational patterns generated by the two genes. Loss of regional heterogeneity in mutagenesis is associated with deficiencies in various DNA repair pathways. These mutation risk redistribution processes modify the mutation supply towards important genes, diverting the course of somatic evolution.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1038/s43018-023-00707-8 |
It is part of: | Nature Cancer, 2024 |
URI: | https://hdl.handle.net/2445/205762 |
Related resource: | https://doi.org/10.1038/s43018-023-00707-8 |
ISSN: | 2662-1347 |
Appears in Collections: | Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) |
Files in This Item:
File | Description | Size | Format | |
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Salvadores_Supek_Nature Cancer_2024.pdf | 3.14 MB | Adobe PDF | View/Open |
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