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The Telomere Length Landscape of Prostate Cancer

View ORCID ProfileJulie Livingstone, View ORCID ProfileYu-Jia Shiah, View ORCID ProfileTakafumi N. Yamaguchi, View ORCID ProfileLawrence E. Heisler, Vincent Huang, View ORCID ProfileRobert Lesurf, Tsumugi Gebo, Benjamin Carlin, View ORCID ProfileStefan Eng, Erik Drysdale, Jeffrey Green, View ORCID ProfileTheodorus van der Kwast, View ORCID ProfileRobert G. Bristow, View ORCID ProfileMichael Fraser, View ORCID ProfilePaul C. Boutros
doi: https://doi.org/10.1101/2021.05.22.445239
Julie Livingstone
1Department of Human Genetics, University of California, Los Angeles, CA 90095, USA
2Department of Urology, University of California, Los Angeles, CA 90024, USA
3Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, CA 90024, USA
4Institute for Precision Health, University of California, Los Angeles, CA 90024, USA
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Yu-Jia Shiah
5Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada
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Takafumi N. Yamaguchi
1Department of Human Genetics, University of California, Los Angeles, CA 90095, USA
2Department of Urology, University of California, Los Angeles, CA 90024, USA
3Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, CA 90024, USA
4Institute for Precision Health, University of California, Los Angeles, CA 90024, USA
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Lawrence E. Heisler
5Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada
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Vincent Huang
5Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada
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Robert Lesurf
5Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada
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  • ORCID record for Robert Lesurf
Tsumugi Gebo
1Department of Human Genetics, University of California, Los Angeles, CA 90095, USA
2Department of Urology, University of California, Los Angeles, CA 90024, USA
3Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, CA 90024, USA
4Institute for Precision Health, University of California, Los Angeles, CA 90024, USA
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Benjamin Carlin
1Department of Human Genetics, University of California, Los Angeles, CA 90095, USA
2Department of Urology, University of California, Los Angeles, CA 90024, USA
3Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, CA 90024, USA
4Institute for Precision Health, University of California, Los Angeles, CA 90024, USA
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Stefan Eng
1Department of Human Genetics, University of California, Los Angeles, CA 90095, USA
2Department of Urology, University of California, Los Angeles, CA 90024, USA
3Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, CA 90024, USA
4Institute for Precision Health, University of California, Los Angeles, CA 90024, USA
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Erik Drysdale
5Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada
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Jeffrey Green
5Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada
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Theodorus van der Kwast
6Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
7Department of Pathology, Laboratory Medicine Program, University Health Network, Toronto, ON M5G 2C4, Canada
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Robert G. Bristow
6Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
8Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada
9Manchester Cancer Research Centre, Manchester, United Kingdom
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Michael Fraser
6Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
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  • ORCID record for Michael Fraser
Paul C. Boutros
1Department of Human Genetics, University of California, Los Angeles, CA 90095, USA
2Department of Urology, University of California, Los Angeles, CA 90024, USA
3Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, CA 90024, USA
4Institute for Precision Health, University of California, Los Angeles, CA 90024, USA
8Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada
10Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5S 1A8, Canada
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  • For correspondence: pboutros@mednet.ucla.edu
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Abstract

Replicative immortality is a hallmark of cancer, and can be achieved through telomere lengthening and maintenance. We report telomere lengths (TLs) of 392 localized prostate cancer tumours and characterize their relationship to genomic, transcriptomic and proteomic features. Shorter tumour TLs were associated with elevated genomic instability, including single-nucleotide variants, indels and structural variants. Genes involved in cell proliferation and signaling were correlated with tumour TL at all levels of the central dogma. TL was also associated with multiple clinical features of a tumour. Longer TLs in non-tumour samples were associated with a lower rate of biochemical relapse after definitive local therapy. Our analysis integrates multi-omics data to illuminate the relationship of specific genomic alterations in a tumour and TL in prostate cancer. Although the role of telomere length in cancer has been well studied, its association to genomic features is less well known. We describe the multi-level integration of telomere length, genomics, transcriptomics and proteomics in localized prostate cancer. Patient Summary We examined the association between telomere length and multiple omics-level data in prostate cancer. We observed that traditional telomere mutations are rare in prostate cancer and that telomere length is associated with multiple measure of genomic instability.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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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
bioRxiv 2021.05.22.445239; doi: https://doi.org/10.1101/2021.05.22.445239
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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
bioRxiv 2021.05.22.445239; doi: https://doi.org/10.1101/2021.05.22.445239

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