Integrated evaluation of telomerase activation and telomere maintenance across cancer cell lines
- University of California, San Francisco, United States
- Broad Institute of Harvard and MIT, United States
Abstract
In cancer, telomere maintenance is critical for the development of replicative immortality. Using genome sequences from the Cancer Cell Line Encyclopedia and Genomics of Drug Sensitivity in Cancer Project, we calculated telomere content across 1,299 cancer cell lines. We find that telomerase reverse transcriptase (TERT) expression correlates with telomere content in lung, central nervous system, and leukemia cell lines. Using CRISPR/Cas9 screening data, we show that lower telomeric content is associated with dependency of CST telomere maintenance genes. Increased dependencies of shelterin members are associated with wild-type TP53 status. Investigating the epigenetic regulation of TERT, we find widespread allele-specific expression in promoter-wildtype contexts. TERT promoter-mutant cell lines exhibit hypomethylation at PRC2-repressed regions, suggesting a cooperative global epigenetic state in the reactivation of telomerase. By incorporating telomere content with genomic features across comprehensively characterized cell lines, we provide further insights into the role of telomere regulation in cancer immortality.
Data availability
Telomere content estimates can be found in the supplementary materials and have been uploaded tothe Cancer Dependency Map portal (https://depmap.org/portal/).
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Cancer Cell Line Encyclopediahttps://doi.org/10.1038/s41586-019-1186-3.
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Quantitative Proteomics of the Cancer Cell Line Encyclopediahttps://doi.org/10.1016/j.cell.2019.12.023.
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DepMap 20Q2 Publichttps://doi.org/10.6084/m9.figshare.12280541.v4.
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GDSC whole-exome sequencing dataEuropean Genome-phenome Archive, EGAS00001000978.
Article and author information
Author details
Funding
Prostate Cancer Foundation (Young Investigator Award)
- Franklin W Huang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- C Daniela Robles-Espinoza, International Laboratory for Human Genome Research, Mexico
Version history
- Received: January 2, 2021
- Preprint posted: January 24, 2021 (view preprint)
- Accepted: August 27, 2021
- Accepted Manuscript published: September 6, 2021 (version 1)
- Version of Record published: October 21, 2021 (version 2)
Copyright
© 2021, Hu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Integrated evaluation of telomerase activation and telomere maintenance across cancer cell lines
eLife 10:e66198.
https://doi.org/10.7554/eLife.66198
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