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

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 <0.00001; n = 27,876) and DNA methylation profiles accurately distinguished between tumor T2E subgroups. A number of top-ranked differentially methylated CpGs in genes (FDR Q-values ≤1.53E-29) were identified: C3orf14, CACNA1D, GREM1, KLK10, NT5C, PDE4D, RAB40C, SEPT9, and TRIB2, several of which had a corresponding alteration in mRNA expression. These genes may have various roles in the pathogenesis of PCa, and the calcium-channel gene CACNA1D is a known ERG-target. Analysis of The Cancer Genome Atlas (TCGA) data provided confirmatory evidence for our findings. 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.

journal_name

Clin Epigenetics

journal_title

Clinical epigenetics

authors

Geybels MS,Alumkal JJ,Luedeke M,Rinckleb A,Zhao S,Shui IM,Bibikova M,Klotzle B,van den Brandt PA,Ostrander EA,Fan JB,Feng Z,Maier C,Stanford JL

doi

10.1186/s13148-015-0161-6

subject

Has Abstract

pub_date

2015-12-12 00:00:00

pages

128

eissn

1868-7075

issn

1868-7083

pii

161

journal_volume

pub_type

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