DNA methylation of the TERT promoter and its impact on human cancer
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 ca...
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| Veröffentlicht in: | Current opinion in genetics & development 2020-02, Vol.60, p.17-24 |
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| creator | Lee, Donghyun D Komosa, Martin Nunes, Nuno Miguel Tabori, Uri |
| description | 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. |
| doi_str_mv | 10.1016/j.gde.2020.02.003 |
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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.</description><identifier>ISSN: 0959-437X</identifier><identifier>EISSN: 1879-0380</identifier><identifier>DOI: 10.1016/j.gde.2020.02.003</identifier><identifier>PMID: 32114294</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>DNA Methylation ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasms - enzymology ; Neoplasms - genetics ; Neoplasms - pathology ; Promoter Regions, Genetic ; Telomerase - genetics ; Telomerase - metabolism ; Telomere ; Telomere Homeostasis</subject><ispartof>Current opinion in genetics & development, 2020-02, Vol.60, p.17-24</ispartof><rights>2020</rights><rights>Copyright © 2020. 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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.</description><subject>DNA Methylation</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Neoplasms - enzymology</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - pathology</subject><subject>Promoter Regions, Genetic</subject><subject>Telomerase - genetics</subject><subject>Telomerase - metabolism</subject><subject>Telomere</subject><subject>Telomere Homeostasis</subject><issn>0959-437X</issn><issn>1879-0380</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1PGzEQhq2KqqSUH8AF-chlt-OPdWxxQgHaSqiVUJC4WcY7Sxxld4PtRcq_r6MAR04zh-d9NfMQcsagZsDUz3X93GLNgUMNvAYQX8iM6bmpQGg4IjMwjamkmD8ek-8prQGAM6a-kWNRpuRGzsji-u8V7TGvdhuXwzjQsaN5hXR5c7-k2zj2Y8ZI3dDSkBMN_db5TAu2mno3UO8Gj_EH-dq5TcLTt3lCHm5vlovf1d2_X38WV3eVl8zkSjcKXasapTTT4qkpC-dz12nZgpCGKSaZdNIY2WgUgnWdUK12xpmCeFDihFwcestdLxOmbPuQPG42bsBxSpYLZbQG3bCCsgPq45hSxM5uY-hd3FkGdu_Orm1xZ_fuLHBb3JXM-Vv99NRj-5F4l1WAywOA5cnXgNEmH7AYaENEn207hk_q_wNNtnvs</recordid><startdate>202002</startdate><enddate>202002</enddate><creator>Lee, Donghyun D</creator><creator>Komosa, Martin</creator><creator>Nunes, Nuno Miguel</creator><creator>Tabori, Uri</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3879-9757</orcidid><orcidid>https://orcid.org/0000-0002-6234-8198</orcidid></search><sort><creationdate>202002</creationdate><title>DNA methylation of the TERT promoter and its impact on human cancer</title><author>Lee, Donghyun D ; Komosa, Martin ; Nunes, Nuno Miguel ; Tabori, Uri</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c419t-856ead65668183b5566227af84d0349161414a499458e331ff36d8a9a9f84c063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>DNA Methylation</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Neoplasms - enzymology</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - pathology</topic><topic>Promoter Regions, Genetic</topic><topic>Telomerase - genetics</topic><topic>Telomerase - metabolism</topic><topic>Telomere</topic><topic>Telomere Homeostasis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Donghyun D</creatorcontrib><creatorcontrib>Komosa, Martin</creatorcontrib><creatorcontrib>Nunes, Nuno Miguel</creatorcontrib><creatorcontrib>Tabori, Uri</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Current opinion in genetics & development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Donghyun D</au><au>Komosa, Martin</au><au>Nunes, Nuno Miguel</au><au>Tabori, Uri</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA methylation of the TERT promoter and its impact on human cancer</atitle><jtitle>Current opinion in genetics & development</jtitle><addtitle>Curr Opin Genet Dev</addtitle><date>2020-02</date><risdate>2020</risdate><volume>60</volume><spage>17</spage><epage>24</epage><pages>17-24</pages><issn>0959-437X</issn><eissn>1879-0380</eissn><abstract>Telomere maintenance is a hallmark of human cancer that enables replicative immortality. 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| subjects | DNA Methylation Gene Expression Regulation, Neoplastic Humans Neoplasms - enzymology Neoplasms - genetics Neoplasms - pathology Promoter Regions, Genetic Telomerase - genetics Telomerase - metabolism Telomere Telomere Homeostasis |
| title | DNA methylation of the TERT promoter and its impact on human cancer |
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