TERT-Regulation and Roles in Cancer Formation

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2020 Dec 17

PMID 33329574

Citations 110

Authors

Marta Dratwa

Barbara Wysoczanska

Piotr Lacina

Tomasz Kubik

Katarzyna Bogunia-Kubik

Affiliations

Soon will be listed here.

Abstract

Telomerase reverse transcriptase (TERT) is a catalytic subunit of telomerase. Telomerase complex plays a key role in cancer formation by telomere dependent or independent mechanisms. Telomere maintenance mechanisms include complex changes such as gene amplifications, structural variants, promoter germline and somatic mutations, epigenetic changes, and alternative lengthening of telomere. All of them are cancer specific at tissue histotype and at single cell level expression is regulated in tumors multiple genetic and epigenetic alterations which affect telomerase activity. Telomerase activity expression has an impact on telomere length and can be a useful marker in diagnosis and prognosis of various cancers and a new therapy approach. In this review we want to highlight the main roles of in different mechanisms of cancer development and regulation.

Citing Articles

Telomere length and telomerase reverse transcriptase gene polymorphism as potential markers of complete chimerism and GvHD development after allogeneic haematopoietic stem cell transplantation.

Dratwa-Kuzmin M, Lacina P, Wysoczanska B, Kilinska D, Siemaszko J, Sobczyk-Kruszelnicka M J Cancer Res Clin Oncol. 2025; 151(3):109.

PMID: 40082305 PMC: 11906511. DOI: 10.1007/s00432-025-06160-7.

Identification of telomere-related gene subtypes and prognostic signatures in osteosarcoma.

Song Z, Yu W, Yin X Front Pharmacol. 2025; 16:1545913.

PMID: 40070565 PMC: 11893505. DOI: 10.3389/fphar.2025.1545913.

Canonical and non-canonical functions of the non-coding RNA component (TERC) of telomerase complex.

Cao C, Gong W, Shuai Y, Rasouli S, Ge Q, Khan A Cell Biosci. 2025; 15(1):30.

PMID: 40025596 PMC: 11871756. DOI: 10.1186/s13578-025-01367-0.

Telomeres and telomerase in mesothelioma: Pathophysiology, biomarkers and emerging therapeutic strategies (Review).

Andreikos D, Spandidos D, Georgakopoulou V Int J Oncol. 2025; 66(3).

PMID: 39981889 PMC: 11844339. DOI: 10.3892/ijo.2025.5729.

The impact of C216T and hot spot mutations of the TERT promoter on the clinicopathologic characteristics and S100A10 expression in papillary thyroid carcinoma: a comparative study.

Li P, Huang C, Liu X, Gui H, Li J Diagn Pathol. 2025; 20(1):15.

PMID: 39934880 PMC: 11816782. DOI: 10.1186/s13000-025-01613-6.

References

Baylin S, Jones P . A decade of exploring the cancer epigenome - biological and translational implications. Nat Rev Cancer. 2011; 11(10):726-34. PMC: 3307543. DOI: 10.1038/nrc3130. View

Carcano F, Vidal D, van Helvoort Lengert A, Scapulatempo Neto C, Queiroz L, Marques H . Hotspot TERT promoter mutations are rare events in testicular germ cell tumors. Tumour Biol. 2015; 37(4):4901-7. DOI: 10.1007/s13277-015-4317-y. View

Chiba K, Johnson J, Vogan J, Wagner T, Boyle J, Hockemeyer D . Cancer-associated TERT promoter mutations abrogate telomerase silencing. Elife. 2015; 4. PMC: 4507476. DOI: 10.7554/eLife.07918. View

Seynnaeve B, Lee S, Borah S, Park Y, Pappo A, Kirkwood J . Genetic and Epigenetic Alterations of TERT Are Associated with Inferior Outcome in Adolescent and Young Adult Patients with Melanoma. Sci Rep. 2017; 7:45704. PMC: 5381111. DOI: 10.1038/srep45704. View

Huang F, Hodis E, Xu M, Kryukov G, Chin L, Garraway L . Highly recurrent TERT promoter mutations in human melanoma. Science. 2013; 339(6122):957-9. PMC: 4423787. DOI: 10.1126/science.1229259. View

Lew A, Kellermayer T, Sule B, Szigeti K . Copy Number Variations in Adult-onset Neuropsychiatric Diseases. Curr Genomics. 2018; 19(6):420-430. PMC: 6128389. DOI: 10.2174/1389202919666180330153842. View

Hisatomi H, Ohyashiki K, Ohyashiki J, Nagao K, Kanamaru T, Hirata H . Expression profile of a gamma-deletion variant of the human telomerase reverse transcriptase gene. Neoplasia. 2003; 5(3):193-7. PMC: 1502410. DOI: 10.1016/S1476-5586(03)80051-9. View

McKelvey B, Gilpatrick T, Wang Y, Timp W, Umbricht C, Zeiger M . Characterization of Allele-Specific Regulation of Telomerase Reverse Transcriptase in Promoter Mutant Thyroid Cancer Cell Lines. Thyroid. 2020; 30(10):1470-1481. PMC: 7583328. DOI: 10.1089/thy.2020.0055. View

Matsuguma M, Yujiri T, Yamamoto K, Kajimura Y, Tokunaga Y, Tanaka M . TERT and JAK2 polymorphisms define genetic predisposition to myeloproliferative neoplasms in Japanese patients. Int J Hematol. 2019; 110(6):690-698. DOI: 10.1007/s12185-019-02742-7. View

10.

Stephens P, McBride D, Lin M, Varela I, Pleasance E, Simpson J . Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature. 2009; 462(7276):1005-10. PMC: 3398135. DOI: 10.1038/nature08645. View

11.

Rahman M, Brane A, Tollefsbol T . MicroRNAs and Epigenetics Strategies to Reverse Breast Cancer. Cells. 2019; 8(10). PMC: 6829616. DOI: 10.3390/cells8101214. View

12.

Liu R, Bishop J, Zhu G, Zhang T, Ladenson P, Xing M . Mortality Risk Stratification by Combining BRAF V600E and TERT Promoter Mutations in Papillary Thyroid Cancer: Genetic Duet of BRAF and TERT Promoter Mutations in Thyroid Cancer Mortality. JAMA Oncol. 2016; 3(2):202-208. DOI: 10.1001/jamaoncol.2016.3288. View

13.

Han Y, San-Marina S, Yang L, Khoury H, Minden M . The zinc finger domain of Wilms' tumor 1 suppressor gene (WT1) behaves as a dominant negative, leading to abrogation of WT1 oncogenic potential in breast cancer cells. Breast Cancer Res. 2007; 9(4):R43. PMC: 2206716. DOI: 10.1186/bcr1743. View

14.

Liu L, Lai S, Andrews L, Tollefsbol T . Genetic and epigenetic modulation of telomerase activity in development and disease. Gene. 2004; 340(1):1-10. DOI: 10.1016/j.gene.2004.06.011. View

15.

Aramburu T, Plucinsky S, Skordalakes E . POT1-TPP1 telomere length regulation and disease. Comput Struct Biotechnol J. 2020; 18:1939-1946. PMC: 7385035. DOI: 10.1016/j.csbj.2020.06.040. View

16.

Chau M, El Touny L, Jagadeesh S, Banerjee P . Physiologically achievable concentrations of genistein enhance telomerase activity in prostate cancer cells via the activation of STAT3. Carcinogenesis. 2007; 28(11):2282-90. DOI: 10.1093/carcin/bgm148. View

17.

de Martino M, Taus C, Lucca I, Hofbauer S, Haitel A, Shariat S . Association of human telomerase reverse transcriptase gene polymorphisms, serum levels, and telomere length with renal cell carcinoma risk and pathology. Mol Carcinog. 2015; 55(10):1458-66. DOI: 10.1002/mc.22388. View

18.

Wysoczanska B, Dratwa M, Gebura K, Mizgala J, Mazur G, Wrobel T . Variability within the human gene, telomere length and predisposition to chronic lymphocytic leukemia. Onco Targets Ther. 2019; 12:4309-4320. PMC: 6551596. DOI: 10.2147/OTT.S198313. View

19.

Guilleret I, Yan P, Grange F, Braunschweig R, Bosman F, Benhattar J . Hypermethylation of the human telomerase catalytic subunit (hTERT) gene correlates with telomerase activity. Int J Cancer. 2002; 101(4):335-41. DOI: 10.1002/ijc.10593. View

20.

Lam G, Xian R, Li Y, Burns K, Beemon K . Lack of TERT Promoter Mutations in Human B-Cell Non-Hodgkin Lymphoma. Genes (Basel). 2016; 7(11). PMC: 5126779. DOI: 10.3390/genes7110093. View