Understanding TERT promoter mutations: A common path to immortality

Robert J.A. Bell, H. Tomas Rube, Ana Xavier-Magalhães, Bruno M. Costa, Andrew Mancini, Jun S. Song, Joseph F. Costello

Research output: Contribution to journalReview article

Abstract

Telomerase (TERT) activation is a fundamental step in tumorigenesis. By maintaining telomere length, telomerase relieves a main barrier on cellular lifespan, enabling limitless proliferation driven by oncogenes. The recently discovered, highly recurrent mutations in the promoter of TERT are found in over 50 cancer types, and are the most common mutation in many cancers. Transcriptional activation of TERT, via promoter mutation or other mechanisms, is the rate-limiting step in production of active telomerase. Although TERT is expressed in stem cells, it is naturally silenced upon differentiation. Thus, the presence of TERT promoter mutations may shed light on whether a particular tumor arose from a stem cell or more differentiated cell type. It is becoming clear that TERT mutations occur early during cellular transformation, and activate the TERT promoter by recruiting transcription factors that do not normally regulate TERT gene expression. This review highlights the fundamental and widespread role of TERT promoter mutations in tumorigenesis, including recent progress on their mechanism of transcriptional activation. These somatic promoter mutations, along with germline variation in the TERT locus also appear to have significant value as biomarkers of patient outcome. Understanding the precise molecular mechanism of TERT activation by promoter mutation and germline variation may inspire novel cancer cell-specific targeted therapies for a large number of cancer patients.

Original languageEnglish (US)
Pages (from-to)315-323
Number of pages9
JournalMolecular Cancer Research
Volume14
Issue number4
DOIs
StatePublished - Apr 2016

Fingerprint

Mutation
Telomerase
Neoplasms
Transcriptional Activation
Carcinogenesis
Stem Cells
Germ-Line Mutation
Telomere
Oncogenes
Transcription Factors
Biomarkers
Gene Expression
Therapeutics

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Bell, R. J. A., Rube, H. T., Xavier-Magalhães, A., Costa, B. M., Mancini, A., Song, J. S., & Costello, J. F. (2016). Understanding TERT promoter mutations: A common path to immortality. Molecular Cancer Research, 14(4), 315-323. https://doi.org/10.1158/1541-7786.MCR-16-0003

Understanding TERT promoter mutations : A common path to immortality. / Bell, Robert J.A.; Rube, H. Tomas; Xavier-Magalhães, Ana; Costa, Bruno M.; Mancini, Andrew; Song, Jun S.; Costello, Joseph F.

In: Molecular Cancer Research, Vol. 14, No. 4, 04.2016, p. 315-323.

Research output: Contribution to journalReview article

Bell, RJA, Rube, HT, Xavier-Magalhães, A, Costa, BM, Mancini, A, Song, JS & Costello, JF 2016, 'Understanding TERT promoter mutations: A common path to immortality', Molecular Cancer Research, vol. 14, no. 4, pp. 315-323. https://doi.org/10.1158/1541-7786.MCR-16-0003
Bell, Robert J.A. ; Rube, H. Tomas ; Xavier-Magalhães, Ana ; Costa, Bruno M. ; Mancini, Andrew ; Song, Jun S. ; Costello, Joseph F. / Understanding TERT promoter mutations : A common path to immortality. In: Molecular Cancer Research. 2016 ; Vol. 14, No. 4. pp. 315-323.
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