Epigenomic profiling of prostate cancer identifies differentially methylated genes in TMPRSS2:ERG fusion-positive versus fusion-negative tumors

M.S. Geybels*, J.J. Alumkal, M. Luedeke, A. Rinckleb, S. Zhao, I.M. Shui, M. Bibikova, B. Klotzle, P.A. van den Brandt, E.A. Ostrander, J.B. Fan, Z. Feng, C. Maier, J.L. Stanford

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: About half of all prostate cancers harbor the TMPRSS2:ERG (T2E) gene fusion. While T2E-positive and T2E-negative tumors represent specific molecular subtypes of prostate cancer (PCa), previous studies have not yet comprehensively investigated how these tumor subtypes differ at the epigenetic level. We therefore investigated epigenome-wide DNA methylation profiles of PCa stratified by T2E status.

Results: The study included 496 patients with clinically localized PCa who had a radical prostatectomy as primary treatment for PCa. Fluorescence in situ hybridization (FISH) "break-apart" assays were used to determine tumor T2E- fusion status, which showed that 266 patients (53.6 %) had T2E-positive PCa. The study showed global DNA methylation differences between tumor subtypes. A large number of differentially methylated CpG sites were identified (false-discovery rate [FDR] Q-value

Conclusions: This study identified substantial differences in DNA methylation profiles of T2E-positive and T2E-negative tumors, thereby providing further evidence that different underlying oncogenic pathways characterize these molecular subtypes.

Original languageEnglish
Article number128
Number of pages12
JournalClinical epigenetics
Volume7
DOIs
Publication statusPublished - 12 Dec 2015

Keywords

  • DNA methylation
  • CpG site
  • Epigenetics
  • Epigenomic profiling
  • Prostate cancer
  • Gene fusion
  • TMPRSS2
  • ERG
  • Tumor tissue
  • Unsupervised clustering
  • mRNA expression
  • C3orf14
  • CACNA1D
  • GREM1
  • KLK10
  • NT5C
  • PDE4D
  • RAB40C
  • SEPT9
  • TRIB2
  • TCGA
  • IN-SITU HYBRIDIZATION
  • DNA METHYLATION
  • BODY METHYLATION
  • ERG-EXPRESSION
  • ST ARRAYS
  • ASSOCIATION
  • TARGET
  • TISSUE
  • HYPERMETHYLATION
  • REARRANGEMENTS

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