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 Eng; Erik Drysdale; Jeffrey Green; Theodorus van der Kwast; Robert G Bristow; Michael Fraser; Paul C Boutros

doi:10.1038/s41467-021-27223-6

The telomere length landscape of prostate cancer

Nat Commun. 2021 Nov 25;12(1):6893. doi: 10.1038/s41467-021-27223-6.

Authors

Julie Livingstone^{1

2

3

4}, Yu-Jia Shiah⁵, Takafumi N Yamaguchi^{1

2

3

4}, Lawrence E Heisler⁵, Vincent Huang⁵, Robert Lesurf⁵, Tsumugi Gebo^{1

2

3

4}, Benjamin Carlin^{1

2

3

4}, Stefan Eng^{1

2

3

4}, Erik Drysdale⁵, Jeffrey Green⁵, Theodorus van der Kwast^{6

7}, Robert G Bristow^{6

8

9}, Michael Fraser⁶, Paul C Boutros^{10

11

12

13

14

15}

Affiliations

¹ Department of Human Genetics, University of California, Los Angeles, CA, 90095, USA.
² Department of Urology, University of California, Los Angeles, CA, 90024, USA.
³ Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, CA, 90024, USA.
⁴ Institute for Precision Health, University of California, Los Angeles, CA, 90024, USA.
⁵ Ontario Institute for Cancer Research, Toronto, ON, M5G 0A3, Canada.
⁶ Princess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 2M9, Canada.
⁷ Department of Pathology, Laboratory Medicine Program, University Health Network, Toronto, ON, M5G 2C4, Canada.
⁸ Department of Medical Biophysics, University of Toronto, Toronto, ON, M5G 1L7, Canada.
⁹ Manchester Cancer Research Centre, Manchester, UK.
¹⁰ Department of Human Genetics, University of California, Los Angeles, CA, 90095, USA. pboutros@mednet.ucla.edu.
¹¹ Department of Urology, University of California, Los Angeles, CA, 90024, USA. pboutros@mednet.ucla.edu.
¹² Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, CA, 90024, USA. pboutros@mednet.ucla.edu.
¹³ Institute for Precision Health, University of California, Los Angeles, CA, 90024, USA. pboutros@mednet.ucla.edu.
¹⁴ Department of Medical Biophysics, University of Toronto, Toronto, ON, M5G 1L7, Canada. pboutros@mednet.ucla.edu.
¹⁵ Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, M5S 1A8, Canada. pboutros@mednet.ucla.edu.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

DNA Copy Number Variations
Epigenome
Gene Fusion
Genomics
Humans
Male
Prostatic Neoplasms / genetics*
Prostatic Neoplasms / metabolism
Prostatic Neoplasms / pathology
Proteome
Telomerase / genetics
Telomerase / metabolism
Telomere / genetics*
Transcriptome

Substances

Proteome
TERT protein, human
Telomerase

Abstract

Publication types

MeSH terms

Substances

Grants and funding