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MP37-11 TERT PROMOTER METHYLATION IS A PAN-CANCER BIOMARKER WITH PROGNOSTIC SIGNIFICANCE IN PROSTATE CANCER PATIENTS

2015; Lippincott Williams & Wilkins; Volume: 193; Issue: 4S Linguagem: Inglês

10.1016/j.juro.2015.02.1274

1527-3792

Ricardo Leão, Pedro Castelo‐Branco, Tatiana Lipman, Brittany Campbell, Aryeh J. Price, Cindy Zhang, Ana Gomes, Hugo Coelho, Robert G. Bristow, Michal R. Schweiger, Robert J. Hamilton, Alexandre R. Zlotta, Arnaldo Figueiredo, Helmut Klocker, Holger Sulttmann, Uri Tabori,

Prostate Cancer Diagnosis and Treatment

You have accessJournal of UrologyProstate Cancer: Basic Research I1 Apr 2015MP37-11 TERT PROMOTER METHYLATION IS A PAN-CANCER BIOMARKER WITH PROGNOSTIC SIGNIFICANCE IN PROSTATE CANCER PATIENTS Ricardo Leao, Pedro Castelo-Branco, Tatiana Lipman, Brittany Campbell, Aryeh Price, Cindy Zhang, Ana Gomes, Hugo Coelho, Robert G. Bristow, Michal Schweiger, Robert J. Hamilton, Alexandre R. Zlotta, Arnaldo Figueiredo, Helmut Klocker, Holger Sulttmann, and Uri Tabori Ricardo LeaoRicardo Leao More articles by this author , Pedro Castelo-BrancoPedro Castelo-Branco More articles by this author , Tatiana LipmanTatiana Lipman More articles by this author , Brittany CampbellBrittany Campbell More articles by this author , Aryeh PriceAryeh Price More articles by this author , Cindy ZhangCindy Zhang More articles by this author , Ana GomesAna Gomes More articles by this author , Hugo CoelhoHugo Coelho More articles by this author , Robert G. BristowRobert G. Bristow More articles by this author , Michal SchweigerMichal Schweiger More articles by this author , Robert J. HamiltonRobert J. Hamilton More articles by this author , Alexandre R. ZlottaAlexandre R. Zlotta More articles by this author , Arnaldo FigueiredoArnaldo Figueiredo More articles by this author , Helmut KlockerHelmut Klocker More articles by this author , Holger SulttmannHolger Sulttmann More articles by this author , and Uri TaboriUri Tabori More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1274AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Biomarkers to differentiate between indolent and aggressive prostate tumors are an important unmet need. We uncovered a region in TERT promoter, which is specifically hypermethylated and associated with telomerase activation in cancer tissue. THOR (TERT Hypermethylated Oncological Region) predicted progression and survival in several paediatric cancers. Here we examined the role of THOR as a diagnostic and prognostic biomarker in prostate cancer (PCa) METHODS To test the status of THOR we first used The Cancer Genome Atlas data (TCGA) and analyzed different cancers across 3054 patients. MEDCHIP Seq analysis was used to evaluate normal and malignant tissue in the same specimen. Prognostic role of THOR was assessed in 2 cohorts, from 3 countries (Discovery Cohort (DC), n=164; Validation Cohort (VC), n=103) comprising patients who underwent radical prostatectomy. THOR status was assessed using pyrosequencing. Statistical analysis were done to compare THOR methylation and biochemical progression free survival (BPFS) RESULTS All cancers analyzed (including prostate cancer (n=300)) revealed high THOR methylation (TCGA data). MEDCHIP Seq analysis revealed that THOR is the only region in the TERT gene differentially methylated between normal and malignant prostate tissue (n=50, p<0.0001). THOR methylation is correlated with Gleason (p=0.0082) but not with PSA (p=0.71). THOR hypermethylation was associated with tumor invasiveness and lymph node involvement (p=0.0147 and p=0.031, respectively). BPFS at 5 years was 82% and 64%, and 82% and 33.6% at 8 years (p=0.0263), for THOR hypermethylated and hypomethylated cancers respectively. Similar differences in BPFS were noted in the validation cohort (p=0.0297). Restricting analyses to Gleason 6 tumors, or Gleason 6 and 7 revealed similar survival benefit at 8 years for hypomethylated cancers (p=0.0167 and p=0.0161). In patients with Gleason 6 and 7 cancers, on multivariate analysis THOR was demonstrated as an independent risk factor for recurrence (HR: 2.158, p=0.042). Finally, we explored the ability of THOR to predict recurrence and found that across all PSA levels, patients with THOR hypermethylation were more likely to recur than those with THOR hypomethylation (OR 2.5, p=0.02) CONCLUSIONS THOR is a novel biomarker for prostate cancer, able to independently predict outcome. It adds significant prognostic information to current histopathological parameters in both Gleason 6 and 7 PCa patients. Future studies will evaluate THOR usefulness as a non-invasive tool for disease diagnosis and monitoring. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e442 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ricardo Leao More articles by this author Pedro Castelo-Branco More articles by this author Tatiana Lipman More articles by this author Brittany Campbell More articles by this author Aryeh Price More articles by this author Cindy Zhang More articles by this author Ana Gomes More articles by this author Hugo Coelho More articles by this author Robert G. Bristow More articles by this author Michal Schweiger More articles by this author Robert J. Hamilton More articles by this author Alexandre R. Zlotta More articles by this author Arnaldo Figueiredo More articles by this author Helmut Klocker More articles by this author Holger Sulttmann More articles by this author Uri Tabori More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...