TERT promoter mutations and telomerase reactivation in urothelial cancer
Reactivation of telomerase, the chromosome end–replicating enzyme, drives human cell immortality and cancer. Point mutations in the telomerase reverse transcriptase (TERT) gene promoter occur at high frequency in multiple cancers, including urothelial cancer (UC), but their effect on telomerase func...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2015-02, Vol.347 (6225), p.1006-1010 |
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| container_title | Science (American Association for the Advancement of Science) |
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| creator | Borah, Sumit Xi, Linghe Zaug, Arthur J. Powell, Natasha M. Dancik, Garrett M. Cohen, Scott B. Costello, James C. Theodorescu, Dan Cech, Thomas R. |
| description | Reactivation of telomerase, the chromosome end–replicating enzyme, drives human cell immortality and cancer. Point mutations in the telomerase reverse transcriptase (TERT) gene promoter occur at high frequency in multiple cancers, including urothelial cancer (UC), but their effect on telomerase function has been unclear. In a study of 23 human UC cell lines, we show that these promoter mutations correlate with higher levels of TERT messenger RNA (mRNA), TERT protein, telomerase enzymatic activity, and telomere length. Although previous studies found no relation between TERT promoter mutations and UC patient outcome, we find that elevated TERT mRNA expression strongly correlates with reduced disease-specific survival in two independent UC patient cohorts (n = 35; n = 87). These results suggest that high telomerase activity may be a better marker of aggressive UC tumors than TERT promoter mutations alone. |
| doi_str_mv | 10.1126/science.1260200 |
| format | Article |
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Point mutations in the telomerase reverse transcriptase (TERT) gene promoter occur at high frequency in multiple cancers, including urothelial cancer (UC), but their effect on telomerase function has been unclear. In a study of 23 human UC cell lines, we show that these promoter mutations correlate with higher levels of TERT messenger RNA (mRNA), TERT protein, telomerase enzymatic activity, and telomere length. Although previous studies found no relation between TERT promoter mutations and UC patient outcome, we find that elevated TERT mRNA expression strongly correlates with reduced disease-specific survival in two independent UC patient cohorts (n = 35; n = 87). These results suggest that high telomerase activity may be a better marker of aggressive UC tumors than TERT promoter mutations alone.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1260200</identifier><identifier>PMID: 25722414</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington: American Association for the Advancement of Science</publisher><subject>Activation ; Aggression ; Cancer ; Chromosomes ; Downstream effects ; Enzymes ; Mutation ; Mutations ; Patients ; Telomerase</subject><ispartof>Science (American Association for the Advancement of Science), 2015-02, Vol.347 (6225), p.1006-1010</ispartof><rights>Copyright © 2015 American Association for the Advancement of Science</rights><rights>Copyright © 2015, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-b692f9137585423c83b7470a406853757f5033aeda83fbbc8c94590fa32a96433</citedby><cites>FETCH-LOGICAL-c453t-b692f9137585423c83b7470a406853757f5033aeda83fbbc8c94590fa32a96433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/24746226$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/24746226$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,776,780,799,881,2870,2871,27903,27904,57996,58229</link.rule.ids></links><search><creatorcontrib>Borah, Sumit</creatorcontrib><creatorcontrib>Xi, Linghe</creatorcontrib><creatorcontrib>Zaug, Arthur J.</creatorcontrib><creatorcontrib>Powell, Natasha M.</creatorcontrib><creatorcontrib>Dancik, Garrett M.</creatorcontrib><creatorcontrib>Cohen, Scott B.</creatorcontrib><creatorcontrib>Costello, James C.</creatorcontrib><creatorcontrib>Theodorescu, Dan</creatorcontrib><creatorcontrib>Cech, Thomas R.</creatorcontrib><title>TERT promoter mutations and telomerase reactivation in urothelial cancer</title><title>Science (American Association for the Advancement of Science)</title><description>Reactivation of telomerase, the chromosome end–replicating enzyme, drives human cell immortality and cancer. Point mutations in the telomerase reverse transcriptase (TERT) gene promoter occur at high frequency in multiple cancers, including urothelial cancer (UC), but their effect on telomerase function has been unclear. In a study of 23 human UC cell lines, we show that these promoter mutations correlate with higher levels of TERT messenger RNA (mRNA), TERT protein, telomerase enzymatic activity, and telomere length. Although previous studies found no relation between TERT promoter mutations and UC patient outcome, we find that elevated TERT mRNA expression strongly correlates with reduced disease-specific survival in two independent UC patient cohorts (n = 35; n = 87). These results suggest that high telomerase activity may be a better marker of aggressive UC tumors than TERT promoter mutations alone.</description><subject>Activation</subject><subject>Aggression</subject><subject>Cancer</subject><subject>Chromosomes</subject><subject>Downstream effects</subject><subject>Enzymes</subject><subject>Mutation</subject><subject>Mutations</subject><subject>Patients</subject><subject>Telomerase</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqFkc1LJDEQxYO46Kx69iQ0eNlLa-U7uQgi7rogLCyz55DOpDVDd2dM0gP-9xudQVgve6pQ71cvRT2EzjFcYUzEdXbBT85f1TcQgAO0wKB5qwnQQ7QAoKJVIPkx-przGqBqmh6hY8IlIQyzBXpY3v9eNpsUx1h8asa52BLilBs7rZrihzj6ZLNvkreuhO272ISpmVMsz34IdmicrRukU_Slt0P2Z_t6gv58v1_ePbSPv378vLt9bB3jtLSd0KTXmEquOCPUKdpJJsEyEIrXruw5UGr9yirad51TTjOuobeUWC0YpSfoZue7mbvRr5yfSrKD2aQw2vRqog3mX2UKz-Ypbg0T9Q9JqsG3vUGKL7PPxYwhOz8MdvJxzgZrYPWUnLL_owpXWij85nr5CV3HOU31EgYLriTGkopKXe8ol2LOyfcfe2Mwb4GafaBmH2iduNhNrHOJ6QMnTDJBiKB_AWiHnDI</recordid><startdate>20150227</startdate><enddate>20150227</enddate><creator>Borah, Sumit</creator><creator>Xi, Linghe</creator><creator>Zaug, Arthur J.</creator><creator>Powell, Natasha M.</creator><creator>Dancik, Garrett M.</creator><creator>Cohen, Scott B.</creator><creator>Costello, James C.</creator><creator>Theodorescu, Dan</creator><creator>Cech, Thomas R.</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20150227</creationdate><title>TERT promoter mutations and telomerase reactivation in urothelial cancer</title><author>Borah, Sumit ; 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| source | American Association for the Advancement of Science; Jstor Complete Legacy |
| subjects | Activation Aggression Cancer Chromosomes Downstream effects Enzymes Mutation Mutations Patients Telomerase |
| title | TERT promoter mutations and telomerase reactivation in urothelial cancer |
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