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

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

Cite this

Geybels, M. S., Alumkal, J. J., Luedeke, M., Rinckleb, A., Zhao, S., Shui, I. M., Bibikova, M., Klotzle, B., van den Brandt, P. A., Ostrander, E. A., Fan, J. B., Feng, Z., Maier, C., & Stanford, J. L. (2015). Epigenomic profiling of prostate cancer identifies differentially methylated genes in TMPRSS2:ERG fusion-positive versus fusion-negative tumors. Clinical epigenetics, 7, [128]. https://doi.org/10.1186/s13148-015-0161-6