Liddiard, Kate ![]() ![]() ![]() |
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Abstract
Identifying attributes that distinguish pre-malignant from senescent cells provides opportunities for targeted disease eradication and revival of anti-tumour immunity. We modelled a telomere-driven crisis in four human fibroblast lines, sampling at multiple time points to delineate genomic rearrangements and transcriptome developments that characterize the transition from dynamic proliferation into replicative crisis. Progression through crisis was associated with abundant intra-chromosomal telomere fusions with increasing asymmetry and reduced microhomology usage, suggesting shifts in DNA repair capacity. Eroded telomeres also fused with genomic loci actively engaged in transcription, with particular enrichment in long genes. Both gross copy number alterations and transcriptional responses to crisis likely underpin the elevated frequencies of telomere fusion with chromosomes 9, 16, 17, 19 and most exceptionally, chromosome 12. Juxtaposition of crisis-regulated genes with loci undergoing de novo recombination exposes the collusive contributions of cellular stress responses to the evolving cancer genome.
Item Type: | Article |
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Date Type: | Published Online |
Status: | Published |
Schools: | Advanced Research Computing @ Cardiff (ARCCA) Medicine |
Publisher: | Oxford University Press |
ISSN: | 2632-8674 |
Funders: | CRUK |
Date of First Compliant Deposit: | 18 December 2020 |
Date of Acceptance: | 17 December 2020 |
Last Modified: | 23 Jul 2024 16:16 |
URI: | https://orca.cardiff.ac.uk/id/eprint/137117 |
Citation Data
Cited 3 times in Scopus. View in Scopus. Powered By Scopus® Data
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