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  A cancer specific hypermethylation signature of the TERT promoter predicts biochemical relapse in prostate cancer: A retrospective cohort study

Castelo-Branco, P., Leão, R., Lipman, T., Campbell, B., Lee, D., Price, A., et al. (2016). A cancer specific hypermethylation signature of the TERT promoter predicts biochemical relapse in prostate cancer: A retrospective cohort study. Oncotarget, 36(7), 57726-57736. doi:10.18632/oncotarget.10639.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-5E6B-5 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-5E6C-3
Genre: Journal Article

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@ 2016 Impact Journals, LLC

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 Creators:
Castelo-Branco, Pedro , Author
Leão, Ricardo , Author
Lipman, Tatiana , Author
Campbell, Brittany , Author
Lee, Donghyun, Author
Price, Aryeh, Author
Zhang, Cindy , Author
Heidari, Abolfazl, Author
Stephens, Derek , Author
Boerno, Stefan T.1, Author              
Coelho, Hugo, Author
Gomes, Ana, Author
Domingos, Celia , Author
Apolonio, Joana D., Author
Schäfer, Georg, Author
Bristow, Robert G. , Author
Schweiger, Michal R.2, 3, Author              
Hamilton, Robert, Author
Zlotta, Alexandre , Author
Figueiredo, Arnaldo , Author
Helmut, Klocker, AuthorSültmann, Holger , AuthorTabori, Uri, Author more..
Affiliations:
1Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              
2Cancer Genomics (Michal-Ruth Schweiger), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479649              
3Cologne Center for Genomics, Cologne University, Cologne, Germany, ou_persistent22              

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Free keywords: Gleason score; TERT; biomarker; diagnostic; prostate cancer
 Abstract: The identification of new biomarkers to differentiate between indolent and aggressive prostate tumors is an important unmet need. We examined the role of THOR (TERT Hypermethylated Oncological Region) as a diagnostic and prognostic biomarker in prostate cancer (PCa).We analyzed THOR in common cancers using genome-wide methylation arrays. Methylation status of the whole TERT gene in benign and malignant prostate samples was determined by MeDIP-Seq. The prognostic role of THOR in PCa was assessed by pyrosequencing on discovery and validation cohorts from patients who underwent radical prostatectomy with long-term follow-up data.Most cancers (n = 3056) including PCa (n = 300) exhibited hypermethylation of THOR. THOR was the only region within the TERT gene that is differentially methylated between normal and malignant prostate tissue (p < 0.0001). Also, THOR was significantly hypermethylated in PCa when compared to paired benign tissues (n = 164, p < 0.0001). THOR hypermethylation correlated with Gleason scores and was associated with tumor invasiveness (p = 0.0147). Five years biochemical progression free survival (BPFS) for PCa patients in the discovery cohort was 87% (95% CI 73-100) and 65% (95% CI 52-78) for THOR non-hypermethylated and hypermethylated cancers respectively (p = 0.01). Similar differences in BPFS were noted in the validation cohort (p = 0.03). Importantly, THOR was able to predict outcome in the challenging (Gleason 6 and 7 (3 + 4)) PCa (p = 0.007). For this group, THOR was an independent risk factor for BPFS with a hazard-ratio of 3.685 (p = 0.0247). Finally, THOR hypermethylation more than doubled the risk of recurrence across all PSA levels (OR 2.5, p = 0.02).

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Language(s): eng - English
 Dates: 2016-07-16
 Publication Status: Published online
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.18632/oncotarget.10639
 Degree: -

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Title: Oncotarget
Source Genre: Journal
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Publ. Info: Orchard Park, NY : Impact Journals
Pages: - Volume / Issue: 36 (7) Sequence Number: - Start / End Page: 57726 - 57736 Identifier: -