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Systematic analysis of telomere length and somatic alterations in 31 cancer types
Open accessAbstract
Cancer cells survive cellular crisis through telomere maintenance mechanisms. We report telomere lengths in 18,430 samples, including tumors and non-neoplastic samples, across 31 cancer types. Telomeres were shorter in tumors than in normal tissues and longer in sarcomas and gliomas than in other cancers. Among 6,835 cancers, 73% expressed telomerase reverse transcriptase (TERT), which was associated with TERT point mutations, rearrangements, DNA amplifications and transcript fusions and predictive of telomerase activity. TERT promoter methylation provided an additional deregulatory TERT expression mechanism. Five percent of cases, characterized by undetectable TERT expression and alterations in ATRX or DAXX, demonstrated elongated telomeres and increased telomeric repeat-containing RNA (TERRA). The remaining 22% of tumors neither expressed TERT nor harbored alterations in ATRX or DAXX. In this group, telomere length positively correlated with TP53 and RB1 mutations. Our analysis integrates TERT abnormalities, telomerase activity and genomic alterations with telomere length in cancer.
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“Various mechanisms have been identified to alter hTERT gene expression, including methylation of its promoter, mutational changes within the promoter, amplifications, and structural variations [193].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [193]
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Metadata
- Authors
- Barthel, F. P., Wei, W., Tang, M., Martinez-Ledesma, E., Hu, X., Amin, S. B., Akdemir, K. C., Seth, S., Song, X., Wang, Q., Lichtenberg, T., Hu, J., Zhang, J., Zheng, S., & Verhaak, R. G. W.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Nationwide Children's Hospital (US)
- Corresponding author
- Zheng, Siyuan
- Verhaak, Roel G W
- ORCID
- Venue
- Nature Genetics
- Published
- 2017-01-30
- Volume
- 49
- Issue
- 3
- Pages
- 349-357
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC5571729
- OpenAlex
- W2581179619
- Cited by
- 614
- References
- 72
- Citations by year
- 2026: 23 · 2025: 58 · 2024: 72 · 2023: 85 · 2022: 96 · 2021: 92 · 2020: 80 · 2019: 45 · 2018: 41 · 2017: 22
- FWCI
- 38.05
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Cancer Prevention and Research Institute of Texas (R140606)
- McGill University
- Broad Institute
- National Institutes of Health
- University of Texas MD Anderson Cancer Center (P30CA 16672)
- National Cancer Institute (R01CA190121, P01CA085878, U24CA143883, P30CA016672, P50CA127001, P30CA034196)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- telomere length, telomere maintenance, telomerase reverse transcriptase, TERT mutation, alternative lengthening of telomeres, ATRX, DAXX, Terra, TP53 mutation, RB1 mutation, sarcoma, glioma, cancer genomics
- MeSH terms
- Glioma, Humans, Neoplasms, Promoter Regions, Genetic, Sarcoma, Tumor Suppressor Protein p53, Telomere, Point Mutation, Telomerase, DNA Methylation, Ubiquitin-Protein Ligases, Retinoblastoma Binding Proteins
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