Prevalence of the Alternative Lengthening of Telomeres Telomere Maintenance Mechanism in Human Cancer Subtypes
Open accessAbstract
Approximately 10% to 15% of human cancers lack detectable telomerase activity, and a subset of these maintain telomere lengths by the telomerase-independent telomere maintenance mechanism termed alternative lengthening of telomeres (ALT). The ALT phenotype, relatively common in subtypes of sarcomas and astrocytomas, has rarely been reported in epithelial malignancies. However, the prevalence of ALT has not been thoroughly assessed across all cancer types. We therefore comprehensively surveyed the ALT phenotype in a broad range of human cancers. In total, two independent sets comprising 6110 primary tumors from 94 different cancer subtypes, 541 benign neoplasms, and 264 normal tissue samples were assessed by combined telomere-specific fluorescence in situ hybridization and immunofluorescence labeling for PML protein. Overall, ALT was observed in 3.73% (228/6110) of all tumor specimens, but was not observed in benign neoplasms or normal tissues. This is the first report of ALT in carcinomas arising from the bladder, cervix, endometrium, esophagus, gallbladder, kidney, liver, and lung. Additionally, this is the first report of ALT in medulloblastomas, oligodendrogliomas, meningiomas, schwannomas, and pediatric glioblastoma multiformes. Previous studies have shown associations between ALT status and prognosis in some tumor types; thus, further studies are warranted to assess the potential prognostic significance and unique biology of ALT-positive tumors. These findings may have therapeutic consequences, because ALT-positive cancers are predicted to be resistant to anti-telomerase therapies.
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ALT is associated with mutations in ATRX in vitro and in several human cancers, including glioblastomas.
“ALT is associated with mutations in the chromatin remodeller α-thalassaemia/mental retardation syndrome X-linked (AT R X ) both in vitro and in several human cancers, including glioblastomas162–165.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [165]
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- Authors
- Heaphy, C. M., Subhawong, A. P., Hong, S.-M., Goggins, M. G., Montgomery, E. A., Gabrielson, E., Netto, G. J., Epstein, J. I., Lotan, T. L., Westra, W. H., Shih, I.-M., Iacobuzio-Donahue, C. A., Maitra, A., Li, Q. K., Eberhart, C. G., Taube, J. M., Rakheja, D., Kurman, R. J., Wu, T. C., Roden, R. B., Argani, P., De Marzo, A. M., Terracciano, L., Torbenson, M., & Meeker, A. K.
- Affiliations
- Johns Hopkins University (US)
- Children's Medical Center (US)
- University Hospital of Basel (CH)
- Corresponding author
- Meeker, Alan K.
- ORCID
- Heaphy, Christopher M.
- Hong, Seung-Mo
- Goggins, Michael G.
- Montgomery, Elizabeth A.
- Gabrielson, Edward
- Netto, George J.
- Epstein, Jonathan I.
- Lotan, Tamara L.
- Westra, William H.
- Shih, Ie-Ming
- Maitra, Anirban
- Eberhart, Charles G.
- Taube, Janis M.
- Rakheja, Dinesh
- Roden, Richard B.
- Argani, Pedram
- Terracciano, Luigi
- Torbenson, Michael
- Meeker, Alan K.
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 179
- Issue
- 4
- Pages
- 1608-1615
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC3181356
- OpenAlex
- W2103453025
- Cited by
- 516
- References
- 31
- Citations by year
- 2026: 19 · 2025: 41 · 2024: 29 · 2023: 40 · 2022: 33 · 2021: 44 · 2020: 47 · 2019: 39 · 2018: 35 · 2017: 30 · 2016: 38 · 2015: 43 · 2014: 24 · 2013: 31 · 2012: 21
- FWCI
- 16.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (T32 CA067751)
- National Cancer Institute (P50 CA058184, P50 CA098252, P50 CA58236, P50 CA62924, P50 CA88843)
- California Breast Cancer Research Program (W81XWH-09-1-0650)
- School of Medicine, Johns Hopkins University
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- alternative lengthening of telomeres, telomere maintenance mechanisms, tumor subtypes, epithelial cancers, sarcoma, astrocytoma, PML protein, benign tumors, medulloblastoma, oligodendroglioma, meningioma, schwannoma
- MeSH terms
- Female, Humans, Male, Neoplasms, Telomere, Telomere Homeostasis
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