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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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Additional file 11 of Reliable assessment of telomere maintenance mechanisms in neuroblastoma
Meeser, A., Bartenhagen, C., Werr, L., Hellmann, A.-M., Kahlert, Y., Hemstedt, N., Nürnberg, P., Altmüller, J., Ackermann, S., Hero, B., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21203247
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Additional file 4 of Reliable assessment of telomere maintenance mechanisms in neuroblastoma
Meeser, A., Bartenhagen, C., Werr, L., Hellmann, A.-M., Kahlert, Y., Hemstedt, N., Nürnberg, P., Altmüller, J., Ackermann, S., Hero, B., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21203259
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Additional file 5 of Reliable assessment of telomere maintenance mechanisms in neuroblastoma
Meeser, A., Bartenhagen, C., Werr, L., Hellmann, A.-M., Kahlert, Y., Hemstedt, N., Nürnberg, P., Altmüller, J., Ackermann, S., Hero, B., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21203262
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Additional file 1 of The telomere maintenance mechanism spectrum and its dynamics in gliomas
Kim, S., Chowdhury, T., Yu, H. J., Kahng, J. Y., Lee, C. E., Choi, S. A., Kim, K.-M., Kang, H., Lee, J. H., Lee, S.-T., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20479631
Additional file 6 of Reliable assessment of telomere maintenance mechanisms in neuroblastoma
Meeser, A., Bartenhagen, C., Werr, L., Hellmann, A.-M., Kahlert, Y., Hemstedt, N., Nürnberg, P., Altmüller, J., Ackermann, S., Hero, B., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21203265
Additional file 8 of Reliable assessment of telomere maintenance mechanisms in neuroblastoma
Meeser, A., Bartenhagen, C., Werr, L., Hellmann, A.-M., Kahlert, Y., Hemstedt, N., Nürnberg, P., Altmüller, J., Ackermann, S., Hero, B., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21203271
Additional file 9 of Reliable assessment of telomere maintenance mechanisms in neuroblastoma
Meeser, A., Bartenhagen, C., Werr, L., Hellmann, A.-M., Kahlert, Y., Hemstedt, N., Nürnberg, P., Altmüller, J., Ackermann, S., Hero, B., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21203274
Additional file 10 of Reliable assessment of telomere maintenance mechanisms in neuroblastoma
Meeser, A., Bartenhagen, C., Werr, L., Hellmann, A.-M., Kahlert, Y., Hemstedt, N., Nürnberg, P., Altmüller, J., Ackermann, S., Hero, B., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21203244
Additional file 7 of Reliable assessment of telomere maintenance mechanisms in neuroblastoma
Meeser, A., Bartenhagen, C., Werr, L., Hellmann, A.-M., Kahlert, Y., Hemstedt, N., Nürnberg, P., Altmüller, J., Ackermann, S., Hero, B., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21203268
Clarkson, E., de León, N., Al-dulaimi, S., Tomlinson, I. P. M., Roberts, T. C., & Tomlinson, I. (2025) · medRxiv · doi:10.64898/2025.12.19.25342655
Alqaisi, O., Storme, G. A., Dennis, A., Dibas, M., Sijarina, L., Grabovci, L., Al-Zghoul, S., Yu, E., & Tai, P. (2026) · Current Oncology · doi:10.3390/curroncol33020074 · Cited by 1
HBV Integration in Clinical Management of Hepatocellular Carcinoma by Liquid Biopsy
Lyu, X., Chan, Z., & Ho, D. W.-H. (2026) · Oncology · doi:10.1159/000551214
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Garsuault, D. (2019) · theses.fr (ABES) · doi:10.70675/b7ec8d0fz1565z4bfdz8f5ezad2c36aaffea
Spatio-temporal regulation of telomere recombination during replicative senescence
Aguilera, P. (2018) · theses.fr (ABES) · doi:10.70675/96005af7zd504z47b7z95cbzdb2c49aea036
Billard, P. (2021) · theses.fr (ABES) · doi:10.70675/7d145f6az2700z4c8bzad56z3286d493fb31
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Coopération oncogénique et effets métaboliques de FGF19 dans le carcinome hépatocellulaire
Bedoya, J. U. (2021) · theses.fr (ABES) · doi:10.70675/d2df913bz04e7z457dzb21dzf6ae23303e0c
D’Angiolo, M. (2021) · theses.fr (ABES) · doi:10.70675/b4a54c23z9d95z4c65zac44z6e1809fed4fe
Les mélanomes muqueux canins comme modèle génétique et thérapeutique des mélanomes muqueux humains
Prouteau, A. (2020) · theses.fr (ABES) · doi:10.70675/b9dc1f15z26a2z434az856azc3f2cc489b2e
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Derrien, A. (2021) · theses.fr (ABES) · doi:10.70675/a794a7dfz4352z46f0zb97az064f9ea78e46
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de Nonneville, A. T. (2021) · theses.fr (ABES) · doi:10.70675/81224ebaz7c43z490az9f19zdbedd0a478cb
Seo, D.-S., & Lim, C. (2026) · Scientific Reports · doi:10.1038/s41598-026-47445-2
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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