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

doi:10.1186/s13148-015-0161-6

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 journal › Article › Academic › peer-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 language	English
Article number	128
Number of pages	12
Journal	Clinical epigenetics
Volume	7
Issue number	1
DOIs	https://doi.org/10.1186/s13148-015-0161-6
Publication status	Published - 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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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(1), Article 128. https://doi.org/10.1186/s13148-015-0161-6

@article{6604036110154a2fa91df81fc401da9c,

title = "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-valueConclusions: 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.",

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",

author = "M.S. Geybels and J.J. Alumkal and M. Luedeke and A. Rinckleb and S. Zhao and I.M. Shui and M. Bibikova and B. Klotzle and \{van den Brandt\}, P.A. and E.A. Ostrander and J.B. Fan and Z. Feng and C. Maier and J.L. Stanford",

year = "2015",

month = dec,

day = "12",

doi = "10.1186/s13148-015-0161-6",

language = "English",

volume = "7",

journal = "Clinical epigenetics",

issn = "1868-7083",

publisher = "BioMed Central Ltd",

number = "1",

}

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 2015, 'Epigenomic profiling of prostate cancer identifies differentially methylated genes in TMPRSS2:ERG fusion-positive versus fusion-negative tumors', Clinical epigenetics, vol. 7, no. 1, 128. https://doi.org/10.1186/s13148-015-0161-6

TY - JOUR

T1 - Epigenomic profiling of prostate cancer identifies differentially methylated genes in TMPRSS2:ERG fusion-positive versus fusion-negative tumors

AU - Geybels, M.S.

AU - Alumkal, J.J.

AU - Luedeke, M.

AU - Rinckleb, A.

AU - Zhao, S.

AU - Shui, I.M.

AU - Bibikova, M.

AU - Klotzle, B.

AU - van den Brandt, P.A.

AU - Ostrander, E.A.

AU - Fan, J.B.

AU - Feng, Z.

AU - Maier, C.

AU - Stanford, J.L.

PY - 2015/12/12

Y1 - 2015/12/12

N2 - 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-valueConclusions: 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.

AB - 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-valueConclusions: 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.

KW - DNA methylation

KW - CpG site

KW - Epigenetics

KW - Epigenomic profiling

KW - Prostate cancer

KW - Gene fusion

KW - TMPRSS2

KW - ERG

KW - Tumor tissue

KW - Unsupervised clustering

KW - mRNA expression

KW - C3orf14

KW - CACNA1D

KW - GREM1

KW - KLK10

KW - NT5C

KW - PDE4D

KW - RAB40C

KW - SEPT9

KW - TRIB2

KW - TCGA

KW - IN-SITU HYBRIDIZATION

KW - DNA METHYLATION

KW - BODY METHYLATION

KW - ERG-EXPRESSION

KW - ST ARRAYS

KW - ASSOCIATION

KW - TARGET

KW - TISSUE

KW - HYPERMETHYLATION

KW - REARRANGEMENTS

UR - https://springernature.figshare.com/articles/dataset/Additional_file_1_of_Epigenomic_profiling_of_prostate_cancer_identifies_differentially_methylated_genes_in_TMPRSS2_ERG_fusion-positive_versus_fusion-negative_tumors/4342934/1

U2 - 10.1186/s13148-015-0161-6

DO - 10.1186/s13148-015-0161-6

M3 - Article

C2 - 26692910

SN - 1868-7083

VL - 7

JO - Clinical epigenetics

JF - Clinical epigenetics

IS - 1

M1 - 128

ER -

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

Abstract

Keywords

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