Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.1/9293
Título: A cancer specific hypermethylation signature of the TERT promoter predicts biochemical relapse in prostate cancer: A retrospective cohort study
Autor: Castelo-Branco, Pedro
Leao, Ricardo
Lipman, Tatiana
Campbell, Brittany
Lee, Donghyun
Price, Aryeh
Zhang, Cindy
Heidari, Abolfazl
Stephens, Derek
Boerno, Stefan
Coelho, Hugo
Gomes, Ana
Domingos, Celia
Apolonio, Joana D.
Schaefer, Georg
Bristow, Robert G.
Schweiger, Michal R.
Hamilton, Robert
Zlotta, Alexandre
Figueiredo, Arnaldo
Klocker, Helmut
Sueltmann, Holger
Tabori, Uri
Data: Set-2016
Editora: Impact Journals
Resumo: 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).
Peer review: yes
URI: http://hdl.handle.net/10400.1/9293
DOI: 10.18632/oncotarget.10639
ISSN: 1949-2553
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