Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.1/9293
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dc.contributor.authorCastelo-Branco, Pedro-
dc.contributor.authorLeao, Ricardo-
dc.contributor.authorLipman, Tatiana-
dc.contributor.authorCampbell, Brittany-
dc.contributor.authorLee, Donghyun-
dc.contributor.authorPrice, Aryeh-
dc.contributor.authorZhang, Cindy-
dc.contributor.authorHeidari, Abolfazl-
dc.contributor.authorStephens, Derek-
dc.contributor.authorBoerno, Stefan-
dc.contributor.authorCoelho, Hugo-
dc.contributor.authorGomes, Ana-
dc.contributor.authorDomingos, Celia-
dc.contributor.authorApolonio, Joana D.-
dc.contributor.authorSchaefer, Georg-
dc.contributor.authorBristow, Robert G.-
dc.contributor.authorSchweiger, Michal R.-
dc.contributor.authorHamilton, Robert-
dc.contributor.authorZlotta, Alexandre-
dc.contributor.authorFigueiredo, Arnaldo-
dc.contributor.authorKlocker, Helmut-
dc.contributor.authorSueltmann, Holger-
dc.contributor.authorTabori, Uri-
dc.description.abstractThe 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).-
dc.publisherImpact Journals-
dc.titleA cancer specific hypermethylation signature of the TERT promoter predicts biochemical relapse in prostate cancer: A retrospective cohort study-
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