The impact of telomere length on prostate cancer aggressiveness, genomic instability and health disparities
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Authors
Huang, R.Bornman, M. S. R.
Stricker, P. D.
Simoni Brum, I.
Mutambirwa, S. B. A.
Jaratlerdsiri, W.
Hayes, Vanessa M
Affiliation
Manchester Cancer Research Centre, University of Manchester, Manchester, M20 4GJ, UK.Issue Date
2024
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Show full item recordAbstract
The telomere repetitive TTAGGG motif at the ends of chromosomes, serves to preserve genomic integrity and chromosomal stability. In turn, genomic instability is a hallmark of cancer-implicating telomere disturbance. Prostate cancer (PCa) shows significant ancestral disparities, with men of African ancestry at the greatest risk for aggressive disease and associated genomic instability. Yet, no study has explored the role of telomere length (TL) with respect to ancestrally driven PCa health disparities. Patient- and technically-matched tumour-blood whole genome sequencing data for 179 ancestrally defined treatment naïve PCa patients (117 African, 62 European), we assessed for TL (blood and tumour) associations. We found shortened tumour TL to be associated with aggressive PCa presentation and elevated genomic instabilities, including percentage of genome alteration and copy number gains, in men of African ancestry. For European patients, tumour TL showed significant associations with PCa driver genes PTEN, TP53, MSH2, SETBP1 and DDX11L1, while shorter blood TL (< 3200 base pairs) and tumour TL (< 2861 base pairs) were correlated with higher risk for biochemical recurrence. Concurring with previous studies linking TL to PCa diagnosis and/or prognosis, for the first time we correlated TL differences with patient ancestry with important implications for future treatments targeting telomere dysfunction.Citation
Huang R, Bornman MSR, Stricker PD, Simoni Brum I, Mutambirwa SBA, Jaratlerdsiri W, et al. The impact of telomere length on prostate cancer aggressiveness, genomic instability and health disparities. Scientific reports. 2024 Apr 2;14(1):7706. PubMed PMID: 38565642. Pubmed Central PMCID: PMC10987561. Epub 2024/04/03. eng.Journal
Scientific ReportsDOI
10.1038/s41598-024-57566-1PubMed ID
38565642Additional Links
https://dx.doi.org/10.1038/s41598-024-57566-1Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41598-024-57566-1