TMPRSS2 fusions with oncogenic ETS factors in prostate cancer involve unbalanced genomic rearrangements and are associated with HDAC1 and epigenetic reprogramming

Kristiina Iljin, Maija Wolf, Henrik Edgren, Santosh Gupta, Sami Kilpinen, Rolf Skotheim, Mari Peltola, Frank Smit, Gerald Verhaegh, Jack Schalken, Matthias Nees, Olli Kallioniemi

Research output: Contribution to journalArticleScientificpeer-review

180 Citations (Scopus)

Abstract

Translocations fusing the strong androgen-responsive gene, TMPRSS2, with ERG or other oncogenic ETS factors may facilitate prostate cancer development. Here, we studied 18 advanced prostate cancers for ETS factor alterations, using reverse transcription-PCR and DNA and RNA array technologies, and identified putative ERG downstream gene targets from the microarray data of 410 prostate samples. Out of the 27 ETS factors, ERG was most frequently overexpressed. Seven cases showed TMPRSS2:ERG gene fusions, whereas the TMPRSS2:ETV4 fusion was seen in one case. In five out of six tumors with high ERG expression, array-CGH analysis revealed interstitial 2.8 Mb deletions between the TMPRSS2 and ERG loci, or smaller, unbalanced rearrangements. In silico analysis of the ERG gene coexpression patterns revealed an association with high expression of the histone deacetylase 1 gene, and low expression of its target genes. Furthermore, we observed increased expression of WNT-associated pathways and down-regulation of tumor necrosis factor and cell death pathways. In summary, our data indicate that the TMPRSS2:ERG translocation is common in advanced prostate cancer and occurs by virtue of unbalanced genomic rearrangements. Activation of ERG by fusion with TMPRSS2 may lead to epigenetic reprogramming, WNT signaling, and down-regulation of cell death pathways, implicating ERG in several hallmarks of cancer with potential therapeutic importance.
Original languageEnglish
Pages (from-to)10242-10246
Number of pages5
JournalCancer Research
Volume66
Issue number21
DOIs
Publication statusPublished - 2006
MoE publication typeA1 Journal article-refereed

Fingerprint

Epigenomics
Prostatic Neoplasms
Genes
Cell Death
Down-Regulation
Histone Deacetylase 1
Gene Fusion
Oligonucleotide Array Sequence Analysis
Computer Simulation
Androgens
Reverse Transcription
Prostate
Neoplasms
Tumor Necrosis Factor-alpha
RNA
Technology
Gene Expression
Polymerase Chain Reaction
Therapeutics

Cite this

Iljin, Kristiina ; Wolf, Maija ; Edgren, Henrik ; Gupta, Santosh ; Kilpinen, Sami ; Skotheim, Rolf ; Peltola, Mari ; Smit, Frank ; Verhaegh, Gerald ; Schalken, Jack ; Nees, Matthias ; Kallioniemi, Olli. / TMPRSS2 fusions with oncogenic ETS factors in prostate cancer involve unbalanced genomic rearrangements and are associated with HDAC1 and epigenetic reprogramming. In: Cancer Research. 2006 ; Vol. 66, No. 21. pp. 10242-10246.
@article{d859e369bd504ef6ab53760dfb3a0f1f,
title = "TMPRSS2 fusions with oncogenic ETS factors in prostate cancer involve unbalanced genomic rearrangements and are associated with HDAC1 and epigenetic reprogramming",
abstract = "Translocations fusing the strong androgen-responsive gene, TMPRSS2, with ERG or other oncogenic ETS factors may facilitate prostate cancer development. Here, we studied 18 advanced prostate cancers for ETS factor alterations, using reverse transcription-PCR and DNA and RNA array technologies, and identified putative ERG downstream gene targets from the microarray data of 410 prostate samples. Out of the 27 ETS factors, ERG was most frequently overexpressed. Seven cases showed TMPRSS2:ERG gene fusions, whereas the TMPRSS2:ETV4 fusion was seen in one case. In five out of six tumors with high ERG expression, array-CGH analysis revealed interstitial 2.8 Mb deletions between the TMPRSS2 and ERG loci, or smaller, unbalanced rearrangements. In silico analysis of the ERG gene coexpression patterns revealed an association with high expression of the histone deacetylase 1 gene, and low expression of its target genes. Furthermore, we observed increased expression of WNT-associated pathways and down-regulation of tumor necrosis factor and cell death pathways. In summary, our data indicate that the TMPRSS2:ERG translocation is common in advanced prostate cancer and occurs by virtue of unbalanced genomic rearrangements. Activation of ERG by fusion with TMPRSS2 may lead to epigenetic reprogramming, WNT signaling, and down-regulation of cell death pathways, implicating ERG in several hallmarks of cancer with potential therapeutic importance.",
author = "Kristiina Iljin and Maija Wolf and Henrik Edgren and Santosh Gupta and Sami Kilpinen and Rolf Skotheim and Mari Peltola and Frank Smit and Gerald Verhaegh and Jack Schalken and Matthias Nees and Olli Kallioniemi",
year = "2006",
doi = "10.1158/0008-5472.CAN-06-1986",
language = "English",
volume = "66",
pages = "10242--10246",
journal = "Cancer Research",
issn = "0008-5472",
number = "21",

}

Iljin, K, Wolf, M, Edgren, H, Gupta, S, Kilpinen, S, Skotheim, R, Peltola, M, Smit, F, Verhaegh, G, Schalken, J, Nees, M & Kallioniemi, O 2006, 'TMPRSS2 fusions with oncogenic ETS factors in prostate cancer involve unbalanced genomic rearrangements and are associated with HDAC1 and epigenetic reprogramming', Cancer Research, vol. 66, no. 21, pp. 10242-10246. https://doi.org/10.1158/0008-5472.CAN-06-1986

TMPRSS2 fusions with oncogenic ETS factors in prostate cancer involve unbalanced genomic rearrangements and are associated with HDAC1 and epigenetic reprogramming. / Iljin, Kristiina; Wolf, Maija; Edgren, Henrik; Gupta, Santosh; Kilpinen, Sami; Skotheim, Rolf; Peltola, Mari; Smit, Frank; Verhaegh, Gerald; Schalken, Jack; Nees, Matthias; Kallioniemi, Olli.

In: Cancer Research, Vol. 66, No. 21, 2006, p. 10242-10246.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - TMPRSS2 fusions with oncogenic ETS factors in prostate cancer involve unbalanced genomic rearrangements and are associated with HDAC1 and epigenetic reprogramming

AU - Iljin, Kristiina

AU - Wolf, Maija

AU - Edgren, Henrik

AU - Gupta, Santosh

AU - Kilpinen, Sami

AU - Skotheim, Rolf

AU - Peltola, Mari

AU - Smit, Frank

AU - Verhaegh, Gerald

AU - Schalken, Jack

AU - Nees, Matthias

AU - Kallioniemi, Olli

PY - 2006

Y1 - 2006

N2 - Translocations fusing the strong androgen-responsive gene, TMPRSS2, with ERG or other oncogenic ETS factors may facilitate prostate cancer development. Here, we studied 18 advanced prostate cancers for ETS factor alterations, using reverse transcription-PCR and DNA and RNA array technologies, and identified putative ERG downstream gene targets from the microarray data of 410 prostate samples. Out of the 27 ETS factors, ERG was most frequently overexpressed. Seven cases showed TMPRSS2:ERG gene fusions, whereas the TMPRSS2:ETV4 fusion was seen in one case. In five out of six tumors with high ERG expression, array-CGH analysis revealed interstitial 2.8 Mb deletions between the TMPRSS2 and ERG loci, or smaller, unbalanced rearrangements. In silico analysis of the ERG gene coexpression patterns revealed an association with high expression of the histone deacetylase 1 gene, and low expression of its target genes. Furthermore, we observed increased expression of WNT-associated pathways and down-regulation of tumor necrosis factor and cell death pathways. In summary, our data indicate that the TMPRSS2:ERG translocation is common in advanced prostate cancer and occurs by virtue of unbalanced genomic rearrangements. Activation of ERG by fusion with TMPRSS2 may lead to epigenetic reprogramming, WNT signaling, and down-regulation of cell death pathways, implicating ERG in several hallmarks of cancer with potential therapeutic importance.

AB - Translocations fusing the strong androgen-responsive gene, TMPRSS2, with ERG or other oncogenic ETS factors may facilitate prostate cancer development. Here, we studied 18 advanced prostate cancers for ETS factor alterations, using reverse transcription-PCR and DNA and RNA array technologies, and identified putative ERG downstream gene targets from the microarray data of 410 prostate samples. Out of the 27 ETS factors, ERG was most frequently overexpressed. Seven cases showed TMPRSS2:ERG gene fusions, whereas the TMPRSS2:ETV4 fusion was seen in one case. In five out of six tumors with high ERG expression, array-CGH analysis revealed interstitial 2.8 Mb deletions between the TMPRSS2 and ERG loci, or smaller, unbalanced rearrangements. In silico analysis of the ERG gene coexpression patterns revealed an association with high expression of the histone deacetylase 1 gene, and low expression of its target genes. Furthermore, we observed increased expression of WNT-associated pathways and down-regulation of tumor necrosis factor and cell death pathways. In summary, our data indicate that the TMPRSS2:ERG translocation is common in advanced prostate cancer and occurs by virtue of unbalanced genomic rearrangements. Activation of ERG by fusion with TMPRSS2 may lead to epigenetic reprogramming, WNT signaling, and down-regulation of cell death pathways, implicating ERG in several hallmarks of cancer with potential therapeutic importance.

U2 - 10.1158/0008-5472.CAN-06-1986

DO - 10.1158/0008-5472.CAN-06-1986

M3 - Article

VL - 66

SP - 10242

EP - 10246

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 21

ER -