Abstract
Replicative immortality is a hallmark of cancer, and can be achieved through telomere lengthening and maintenance. Although the role of telomere length in cancer has been well studied, its association to genomic features is less well known. Here, we report the telomere lengths of 392 localized prostate cancer tumours and characterize their relationship to genomic, transcriptomic and proteomic features. Shorter tumour telomere lengths are associated with elevated genomic instability, including single-nucleotide variants, indels and structural variants. Genes involved in cell proliferation and signaling are correlated with tumour telomere length at all levels of the central dogma. Telomere length is also associated with multiple clinical features of a tumour. Longer telomere lengths in non-tumour samples are associated with a lower rate of biochemical relapse. In summary, we describe the multi-level integration of telomere length, genomics, transcriptomics and proteomics in localized prostate cancer.
Highlights
Replicative immortality is a hallmark of cancer, and can be achieved through telomere lengthening and maintenance
The cohort consisted of 11.2% ISUP Grade Group (GG) 1, 52.8% GG2, 24.6 % GG3, 7.8% GG4 and 3.4% GG5
Since prostate tumour gene expression and clinical behaviour is predominantly driven by CNAs14,19 we investigated their role in telomere length (TL)
Summary
Replicative immortality is a hallmark of cancer, and can be achieved through telomere lengthening and maintenance. We report the telomere lengths of 392 localized prostate cancer tumours and characterize their relationship to genomic, transcriptomic and proteomic features. Localized prostate cancer is a C-class tumour[19], characterized by a paucity of driver single-nucleotide variants (SNVs) and a relatively large number of structural variants (SVs), including copy number aberrations (CNAs) and genomic rearrangements (GRs) Several of these aberrations, including mutations in ATM and amplifications of MYC – which drive DSB repair and cell proliferation, respectively—are associated with significantly reduced time to biochemical and metastatic relapse after local therapy[20]. No well-powered study exists evaluating the association between telomere length, somatic features and clinical outcome in prostate cancer To fill this gap, we quantify the telomere length and somatic mutational landscapes of 392 localized prostate tumours. These data establish the role and regulation of telomere length in localized prostate cancer, and establish clear links between telomere maintenance and drivers of prostate cancer development and clinical aggression
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