Frequency of TERT promoter mutations in primary tumors of the liver
Abstract
Transcriptional regulation of the TERT gene is a major cause of the cancer-specific increase in telomerase activity. Recently, frequent somatic mutations in the TERT promoter have been described in several tumor entities such as melanoma, glioblastoma, bladder cancer, and hepatocellular carcinoma. By generating a putative consensus binding site for ETS transcription factors within the TERT promoter, these mutations are predicted to increase promoter activity and TERT transcription. In order to improve the understanding of the role of TERT promoter mutation in liver tumorigenesis, the mutational status of the TERT promoter was analyzed in 78 hepatocellular carcinomas, 15 hepatocellular adenomas, and 52 intrahepatic cholangiocarciomas. The promoter region of TERT was screened for the two hotspot mutations using PCR and restriction fragment length analysis, utilizing the introduction of novel restriction sites by the somatic mutations. TERT promoter mutation was found in 37 of 78 hepatocellular carcinomas (47 %) and was restricted to the -124C>T mutation. Frequency of mutations was associated with grade of differentiation ranging from 39 % in well-differentiated tumors to 73 % in high-grade hepatocellular carcinomas. TERT promoter mutations were not found in 15 hepatocellular adenomas and 52 intrahepatic cholangiocarcinomas. These data show that TERT promoter mutation is the most frequent genetic alteration in hepatocellular carcinoma known at this time. The striking predominance of the -124C>T mutation compared with other tumor entities suggest a biological difference of the two hotspot mutations. Analysis of TERT promoter mutation might become a diagnostic tool distinguishing hepatocellular adenoma from well-differentiated hepatocellular carcinoma.
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TERT promoter mutations are the most common non-coding mutations in cancer and are found in a growing list of cancers.
“These mutations are the most common mutations in non-coding sequences in cancer and are found in a long, and almost certainly growing, list of cancers153–158.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [157]
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Telomeres in cancer: tumour suppression and genome instability
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- Authors
- Quaas, A., Oldopp, T., Tharun, L., Klingenfeld, C., Krech, T., Sauter, G., & Grob, T. J.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Grob, Tobias J.
- Venue
- Virchows Archiv
- Published
- 2014-09-30
- Volume
- 465
- Issue
- 6
- Pages
- 673-677
- ISSN
- 0945-6317 (ISSN-L)
- 1432-2307
- OpenAlex
- W2120012057
- Cited by
- 70
- References
- 20
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 10 · 2021: 8 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 15 · 2015: 3
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- TERT promoter mutation, hepatocellular carcinoma, hepatocellular adenoma, intrahepatic cholangiocarcinoma, telomerase activation, tumor grade, hepatocarcinogenesis, diagnostic biomarkers
- MeSH terms
- Adenoma, Adolescent, Adult, Aged, Bile Duct Neoplasms, Bile Ducts, Intrahepatic, Child, DNA Mutational Analysis, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, Mutation, Promoter Regions, Genetic, Polymorphism, Restriction Fragment Length, Polymerase Chain Reaction, Cholangiocarcinoma, Telomerase, Young Adult
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