The telomere length landscape of prostate cancer

被引:10
|
作者
Livingstone, Julie [1 ,2 ,3 ,4 ]
Shiah, Yu-Jia [5 ]
Yamaguchi, Takafumi N. [1 ,2 ,3 ,4 ]
Heisler, Lawrence E. [5 ]
Huang, Vincent [5 ]
Lesurf, Robert [5 ]
Gebo, Tsumugi [1 ,2 ,3 ,4 ]
Carlin, Benjamin [1 ,2 ,3 ,4 ]
Eng, Stefan [1 ,2 ,3 ,4 ]
Drysdale, Erik [5 ]
Green, Jeffrey [5 ]
van der Kwast, Theodorus [6 ,7 ]
Bristow, Robert G. [6 ,8 ,9 ]
Fraser, Michael [6 ]
Boutros, Paul C. [1 ,2 ,3 ,4 ,8 ,10 ]
机构
[1] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90024 USA
[3] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA
[4] Univ Calif Los Angeles, Inst Precis Hlth, Los Angeles, CA 90024 USA
[5] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada
[6] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada
[7] Univ Hlth Network, Dept Pathol, Lab Med Program, Toronto, ON M5G 2C4, Canada
[8] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada
[9] Manchester Canc Res Ctr, Manchester, Lancs, England
[10] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON M5S 1A8, Canada
关键词
INTRAEPITHELIAL NEOPLASIA; RNA; RECOMBINATION; VALIDATION; HALLMARKS; PACKAGE;
D O I
10.1038/s41467-021-27223-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Despite the known role of telomere length in cancer, its association with genomic features remains unclear. Here, the authors integrate telomere length, genomics, transcriptomics and proteomics in localized prostate cancer and reveal links between telomere maintenance, disease drivers and clinical outcomes. 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.
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页数:13
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