The telomere length landscape of prostate cancer
Julie Livingstone, Yu-Jia Shiah, Takafumi N. Yamaguchi, Lawrence E. Heisler, Vincent Huang, Robert Lesurf, Tsumugi Gebo, Benjamin Carlin, Stefan E. Eng, Erik Drysdale, Jeffrey Green, Theodorus van der Kwast, Robert G. Bristow, Michael Fraser, Paul C. Boutros
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.