TERT—Regulation and Roles in Cancer Formation

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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 TERT changes such as gene amplifications, TERT structural variants, TERT promoter germline and somatic mutations, TERT epigenetic changes, and alternative lengthening of telomere. All of them are cancer specific at tissue histotype and at single cell level . TERT expression is regulated in tumors via multiple genetic and epigenetic alterations which affect telomerase activity. Telomerase activity via TERT 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 TERT in different mechanisms of cancer development and regulation.

Related collections

Most cited references 213

Record: found
Abstract: found
Article: not found

A decade of exploring the cancer epigenome - biological and translational implications.

Stephen Baylin, Peter A. Jones (2011)

The past decade has highlighted the central role of epigenetic processes in cancer causation, progression and treatment. Next-generation sequencing is providing a window for visualizing the human epigenome and how it is altered in cancer. This view provides many surprises, including linking epigenetic abnormalities to mutations in genes that control DNA methylation, the packaging and the function of DNA in chromatin, and metabolism. Epigenetic alterations are leading candidates for the development of specific markers for cancer detection, diagnosis and prognosis. The enzymatic processes that control the epigenome present new opportunities for deriving therapeutic strategies designed to reverse transcriptional abnormalities that are inherent to the cancer epigenome.

0 comments Cited 404 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Alternative lengthening of telomeres: models, mechanisms and implications.

Anthony J Cesare, Roger R. Reddel (2010)

Unlimited cellular proliferation depends on counteracting the telomere attrition that accompanies DNA replication. In human cancers this usually occurs through upregulation of telomerase activity, but in 10-15% of cancers - including some with particularly poor outcome - it is achieved through a mechanism known as alternative lengthening of telomeres (ALT). ALT, which is dependent on homologous recombination, is therefore an important target for cancer therapy. Although dissection of the mechanism or mechanisms of ALT has been challenging, recent advances have led to the identification of several genes that are required for ALT and the elucidation of the biological significance of some phenotypic markers of ALT. This has enabled development of a rapid assay of ALT activity levels and the construction of molecular models of ALT.

0 comments Cited 377 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Highly recurrent TERT promoter mutations in human melanoma.

Franklin W Huang, Eran Hodis, Mary Jue Xu … (2013)

Systematic sequencing of human cancer genomes has identified many recurrent mutations in the protein-coding regions of genes but rarely in gene regulatory regions. Here, we describe two independent mutations within the core promoter of telomerase reverse transcriptase (TERT), the gene coding for the catalytic subunit of telomerase, which collectively occur in 50 of 70 (71%) melanomas examined. These mutations generate de novo consensus binding motifs for E-twenty-six (ETS) transcription factors, and in reporter assays, the mutations increased transcriptional activity from the TERT promoter by two- to fourfold. Examination of 150 cancer cell lines derived from diverse tumor types revealed the same mutations in 24 cases (16%), with preliminary evidence of elevated frequency in bladder and hepatocellular cancer cells. Thus, somatic mutations in regulatory regions of the genome may represent an important tumorigenic mechanism.

0 comments Cited 326 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Barbara Wysoczańska: URI : https://loop.frontiersin.org/people/1095516

Piotr Łacina: URI : https://loop.frontiersin.org/people/1117039

Katarzyna Bogunia-Kubik: URI : https://loop.frontiersin.org/people/694309

Journal

Journal ID (nlm-ta): Front Immunol

Journal ID (iso-abbrev): Front Immunol

Journal ID (publisher-id): Front. Immunol.

Title: Frontiers in Immunology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-3224

Publication date (Electronic): 19 November 2020

Publication date Collection: 2020

Volume: 11

Electronic Location Identifier: 589929

Affiliations

[1] ¹ Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences , Wroclaw, Poland

[2] ² Department of Computer Engineering, Faculty of Electronics, Wrocław University of Science and Technology , Wroclaw, Poland

Author notes

Edited by: Katherine Chiappinelli, George Washington University, United States

Reviewed by: Yu-Sheng Cong, Hangzhou Normal University, China; Martha Allen Zeiger, National Institutes of Health (NIH), United States

*Correspondence: Marta Dratwa, marta.dratwa@ 123456hirszfeld.pl ; Katarzyna Bogunia-Kubik, katarzyna.bogunia-kubik@ 123456hirszfeld.pl

This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology

Article

DOI: 10.3389/fimmu.2020.589929

PMC ID: 7717964

PubMed ID: 33329574

SO-VID: 48e3bf70-1dee-4de5-9244-3de933a7652b

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 31 July 2020

Date accepted : 16 October 2020

Page count

Figures: 2, Tables: 0, Equations: 0, References: 216, Pages: 16, Words: 7878

Funding

Funded by: Narodowe Centrum Badań i Rozwoju 10.13039/501100005632

Award ID: STRATEGMED3/306853

Comments

Comment on this article

scite_

Smart Citations

Citing PublicationsSupportingMentioningContrasting

View Citations

See how this article has been cited at scite.ai

scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

TERT—Regulation and Roles in Cancer Formation

Read this article at

Abstract

Related collections

Cancer Immunotherapy

Most cited references 213

A decade of exploring the cancer epigenome - biological and translational implications.

Alternative lengthening of telomeres: models, mechanisms and implications.

Highly recurrent TERT promoter mutations in human melanoma.

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Page count

Funding

Categories

Comments

Comment on this article

Similar content 549

Cited by 87

Most referenced authors 3,676