Epigenomic profiling of prostate cancer identifies differentially methylated genes in TMPRSS2

ERG fusion-positive versus fusion-negative tumors

Milan S. Geybels, Joshi Alumkal, Manuel Luedeke, Antje Rinckleb, Shanshan Zhao, Irene M. Shui, Marina Bibikova, Brandy Klotzle, Piet A. van den Brandt, Elaine A. Ostrander, Jian Bing Fan, Ziding Feng, Christiane Maier, Janet L. Stanford

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    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

    Original languageEnglish (US)
    Article number128
    JournalClinical Epigenetics
    Volume7
    Issue number1
    DOIs
    StatePublished - Dec 12 2015

    Fingerprint

    Epigenomics
    Prostatic Neoplasms
    Genes
    Neoplasms
    DNA Methylation
    Gene Fusion
    Prostatectomy
    Fluorescence In Situ Hybridization

    Keywords

    • C3orf14
    • CACNA1D
    • CpG site
    • DNA methylation
    • Epigenetics
    • Epigenomic profiling
    • ERG
    • Gene fusion
    • GREM1
    • KLK10
    • mRNA expression
    • NT5C
    • PDE4D
    • Prostate cancer
    • RAB40C
    • SEPT9
    • TCGA
    • TMPRSS2
    • TRIB2
    • Tumor tissue
    • Unsupervised clustering

    ASJC Scopus subject areas

    • Genetics
    • Molecular Biology
    • Developmental Biology
    • Genetics(clinical)

    Cite this

    Epigenomic profiling of prostate cancer identifies differentially methylated genes in TMPRSS2 : ERG fusion-positive versus fusion-negative tumors. / Geybels, Milan S.; Alumkal, Joshi; Luedeke, Manuel; Rinckleb, Antje; Zhao, Shanshan; Shui, Irene M.; Bibikova, Marina; Klotzle, Brandy; van den Brandt, Piet A.; Ostrander, Elaine A.; Fan, Jian Bing; Feng, Ziding; Maier, Christiane; Stanford, Janet L.

    In: Clinical Epigenetics, Vol. 7, No. 1, 128, 12.12.2015.

    Research output: Contribution to journalArticle

    Geybels, MS, Alumkal, J, 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
    Geybels, Milan S. ; Alumkal, Joshi ; Luedeke, Manuel ; Rinckleb, Antje ; Zhao, Shanshan ; Shui, Irene M. ; Bibikova, Marina ; Klotzle, Brandy ; van den Brandt, Piet A. ; Ostrander, Elaine A. ; Fan, Jian Bing ; Feng, Ziding ; Maier, Christiane ; Stanford, Janet L. / Epigenomic profiling of prostate cancer identifies differentially methylated genes in TMPRSS2 : ERG fusion-positive versus fusion-negative tumors. In: Clinical Epigenetics. 2015 ; Vol. 7, No. 1.
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    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",
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    AU - Luedeke, Manuel

    AU - Rinckleb, Antje

    AU - Zhao, Shanshan

    AU - Shui, Irene M.

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    AU - Klotzle, Brandy

    AU - van den Brandt, Piet A.

    AU - Ostrander, Elaine A.

    AU - Fan, Jian Bing

    AU - Feng, Ziding

    AU - Maier, Christiane

    AU - Stanford, Janet L.

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    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-value

    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-value

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