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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Published in | Science (American Association for the Advancement of Science) Vol. 347; no. 6225; pp. 1006 - 1010 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Washington
American Association for the Advancement of Science
27.02.2015
The American Association for the Advancement of Science |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work. |
ISSN: | 0036-8075 1095-9203 |
DOI: | 10.1126/science.1260200 |