DNA methylation of the TERT promoter and its impact on human cancer

Donghyun D Lee; Martin Komosa; Nuno Miguel Nunes; Uri Tabori

doi:10.1016/j.gde.2020.02.003

DNA methylation of the TERT promoter and its impact on human cancer

Curr Opin Genet Dev. 2020 Feb:60:17-24. doi: 10.1016/j.gde.2020.02.003. Epub 2020 Feb 27.

Authors

Donghyun D Lee¹, Martin Komosa², Nuno Miguel Nunes², Uri Tabori³

Affiliations

¹ Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
² Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
³ Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address: uri.tabori@sickkids.ca.

PMID: 32114294
DOI: 10.1016/j.gde.2020.02.003

Abstract

Telomere maintenance is a hallmark of human cancer that enables replicative immortality. Most cancer cells acquire telomere maintenance by telomerase activation through expression of telomerase reverse transcriptase (TERT), a rate-limiting component of the telomerase holoenzyme. Although multiple cancer-specific genetic alterations such as gain of TERT copy number and recurrent TERT promoter mutations (TPM) have been identified, the majority of cancers still express TERT via unknown mechanisms. In the last decade, DNA methylation of the TERT promoter emerged as a putative epigenetic regulatory mechanism of telomerase activation in cancer. Here, we comparatively discuss studies that investigated the DNA methylation landscape of the TERT promoter. We further review the biological and clinical impacts of TERT promoter hypermethylation in cancer and provide insight into future applications of this phenomenon.

Publication types

Review

MeSH terms

DNA Methylation*
Gene Expression Regulation, Neoplastic*
Humans
Neoplasms / enzymology
Neoplasms / genetics*
Neoplasms / pathology*
Promoter Regions, Genetic
Telomerase / genetics
Telomerase / metabolism*
Telomere Homeostasis*
Telomere*

Substances

TERT protein, human
Telomerase