Paralog dispensability shapes homozygous deletion patterns in tumor genomes.
copy number variation
dispensability
paralogs
robustness
tumor genome evolution
Journal
Molecular systems biology
ISSN: 1744-4292
Titre abrégé: Mol Syst Biol
Pays: England
ID NLM: 101235389
Informations de publication
Date de publication:
06 Dec 2023
06 Dec 2023
Historique:
revised:
24
10
2023
received:
05
09
2023
accepted:
26
10
2023
medline:
7
12
2023
pubmed:
14
11
2023
entrez:
14
11
2023
Statut:
ppublish
Résumé
Genomic instability is a hallmark of cancer, resulting in tumor genomes having large numbers of genetic aberrations, including homozygous deletions of protein coding genes. That tumor cells remain viable in the presence of such gene loss suggests high robustness to genetic perturbation. In model organisms and cancer cell lines, paralogs have been shown to contribute substantially to genetic robustness-they are generally more dispensable for growth than singletons. Here, by analyzing copy number profiles of > 10,000 tumors, we test the hypothesis that the increased dispensability of paralogs shapes tumor genome evolution. We find that genes with paralogs are more likely to be homozygously deleted and that this cannot be explained by other factors known to influence copy number variation. Furthermore, features that influence paralog dispensability in cancer cell lines correlate with paralog deletion frequency in tumors. Finally, paralogs that are broadly essential in cancer cell lines are less frequently deleted in tumors than non-essential paralogs. Overall, our results suggest that homozygous deletions of paralogs are more frequently observed in tumor genomes because paralogs are more dispensable.
Identifiants
pubmed: 37963083
doi: 10.15252/msb.202311987
pmc: PMC10698506
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e11987Subventions
Organisme : Irish Research Council (An Chomhairle um Thaighde in Éirinn)
Organisme : Science Foundation Ireland (SFI)
ID : 20/FFP-P/8641
Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
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