Highly Recurrent TERT Promoter Mutations in Human Melanoma
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Promoter Mutations and Cancer: Cancer genome sequencing projects have highlighted the pathogenic role of recurrent mutations within the protein-coding regions of genes. Now, two studies suggest that the scope of mutations in human tumors extends to gene regulatory regions. In a study of 70 melanomas, Huang et al. (p. 957 , published online 24 January) found that 71% harbored one of two specific mutations in the promoter region of TERT , the gene coding for the catalytic subunit of telomerase, the enzyme that caps chromosome ends. Independently, Horn et al. (p. 959 , published online 24 January) identified a disease-segregating germline mutation in the TERT promoter in a family predisposed to melanoma and found additional TERT promoter mutations in a high percentage of sporadic melanomas and melanoma cell lines. The mutations in both studies generated new binding sites for specific transcription factors and, in reporter assays, caused an increase in transcription.
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Activating mutations in the TERT promoter in several cancer types strongly argue that those tumours were selected for telomerase activation.
“The recent identification of activating mutations in the TERT promoter in several cancer types argues strongly that these tumours had undergone selection for the activation of telomerase57,58.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [57]
Telomerase activation is often accomplished through mutations in the TERT promoter.
“Telomerase activation is often accomplished through mutations in the TERT promoter57,58.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [57]
Mutations that increase expression of telomerase reverse transcriptase (TERT) by two-fold cause large increases in risks of certain cancers.
“Mutations that increase expression of telomerase reverse transcriptase (TERT; the catalytic subunit of telomerase) by two-fold, cause large increases in risks of certain cancers (Horn et al., 2013; Huang et al., 2013).”
From Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging (2015) · cites this paper as Huang et al., 2013
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- Authors
- Huang, F. W., Hodis, E., Xu, M. J., Kryukov, G. V., Chin, L., & Garraway, L. A.
- Affiliations
- Broad Institute (US)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Huang, Franklin W.
- Hodis, Eran
- Garraway, Levi A.
- Venue
- Science
- Published
- 2013-02-22
- Volume
- 339
- Issue
- 6122
- Pages
- 957-959
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4423787
- OpenAlex
- W2104500293
- Cited by
- 1,816
- References
- 11
- Citations by year
- 2026: 51 · 2025: 78 · 2024: 78 · 2023: 106 · 2022: 133 · 2021: 148 · 2020: 161 · 2019: 125 · 2018: 159 · 2017: 166 · 2016: 194 · 2015: 173 · 2014: 149 · 2013: 89 · 2012: 2
- FWCI
- 140.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DP2OD002750)
- National Cancer Institute (R33CA126674, T32CA009172, P01CA163222)
- National Institute of General Medical Sciences (T32 GM07753, T32GM007753)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- TERT promoter mutation, melanoma, telomerase reverse transcriptase, ETS transcription factors, gene regulatory regions, somatic mutations, transcriptional activation, cancer cell lines, bladder cancer, hepatocellular carcinoma, carcinogenesis
- MeSH terms
- Binding Sites, Cell Transformation, Neoplastic, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Melanoma, Mutation, Promoter Regions, Genetic, Transcription, Genetic, Gene Expression Regulation, Neoplastic, Telomerase, Cell Line, Tumor, Proto-Oncogene Proteins c-ets
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