The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation
Open accessAbstract
Background Several somatic mutation hotspots were recently identified in the TERT promoter region in human cancers. Large scale studies of these mutations in multiple tumor types are limited, in particular in Asian populations. This study aimed to: analyze TERT promoter mutations in multiple tumor types in a large Chinese patient cohort, investigate novel tumor types and assess the functional significance of the mutations. Methods TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumor types and 799 tumor tissues from Chinese cancer patients. Thymic epithelial tumors, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by RT-qPCR, telomerase activity by the TRAP assay, and promoter activity by the luciferase reporter assay. Results TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%), and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in GIST, thymic epithelial tumors, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. Conclusions TERT promoter mutations are frequent in multiple tumor types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumorigenesis, making them potential therapeutic targets.
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Frequency of TERT promoter mutations in human cancers
Vinagre, J., Almeida, A., Pópulo, H., Batista, R., Lyra, J., Pinto, V., Coelho, R., Celestino, R., Prazeres, H., Lima, L., et al. (2013) · Nature Communications · doi:10.1038/ncomms3185 · Cited by 898
Trans-ancestry mutational landscape of hepatocellular carcinoma genomes
Totoki, Y., Tatsuno, K., Covington, K. R., Ueda, H., Creighton, C. J., Kato, M., Tsuji, S., Donehower, L. A., Slagle, B. L., Nakamura, H., et al. (2014) · Nature Genetics · doi:10.1038/ng.3126 · Cited by 781
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Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies
Jafri, M. A., Ansari, S. A., Alqahtani, M. H., & Shay, J. W. (2016) · Genome Medicine · doi:10.1186/s13073-016-0324-x · Cited by 716
The Curious Case of the HepG2 Cell Line: 40 Years of Expertise
Arzumanian, V. A., Kiseleva, O. I., & Poverennaya, E. V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222313135 · Cited by 387
Telomeres and Telomere Length: A General Overview
Srinivas, N., Rachakonda, S., & Kumar, R. (2020) · Cancers · doi:10.3390/cancers12030558 · Cited by 304
Isocitrate dehydrogenase mutations in gliomas
Waitkus, M. S., Diplas, B. H., & Yan, H. (2016) · Neuro-Oncology · doi:10.1093/neuonc/nov136 · Cited by 282
Self-citationMechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer
Leão, R., Apolónio, J. D., Lee, D., Figueiredo, A., Tabori, U., & Castelo-Branco, P. (2018) · Journal of Biomedical Science · doi:10.1186/s12929-018-0422-8 · Cited by 265
Metadata
- Authors
- Huang, D.-S., Wang, Z., He, X.-J., Diplas, B. H., Yang, R., Killela, P. J., Meng, Q., Ye, Z.-Y., Wang, W., Jiang, X.-T., Xu, L., He, X.-L., Zhao, Z.-S., Xu, W.-J., Wang, H.-J., Ma, Y.-Y., Xia, Y.-J., Li, L., Zhang, R.-X., Jin, T., Zhao, Z.-K., Xu, J., Yu, S., Wu, F., Liang, J., Wang, S., Jiao, Y., Yan, H., & Tao, H.-Q.
- Venue
- European Journal of Cancer
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 51
- Issue
- 8
- Pages
- 969-976
- ISSN
- 0959-8049 (ISSN-L)
- OpenAlex
- W2105401493
- Cited by
- 193
- References
- 2
- FWCI
- 14.63
- Type
- journal article
- Language
- en
- Open access
- green
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- Huang, D.-S., Wang, Z., He, X.-J., Diplas, B. H., Yang, R., Killela, P. J., Meng, Q., Ye, Z.-Y., Wang, W., Jiang, X.-T., Xu, L., He, X.-L., Zhao, Z.-S., Xu, W.-J., Wang, H.-J., Ma, Y.-Y., Xia, Y.-J., Li, L., Zhang, R.-X., . . . Tao, H.-Q. (2015). Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation. European Journal of Cancer. https://doi.org/10.1016/j.ejca.2015.03.010
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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