TMPRSS2: ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer

Sven Perner, Francesca Demichelis, Rameen Beroukhim, Folke H. Schmidt, Juan Miguel Mosquera, Sunita Setlur, Joelle Tchinda, Scott A. Tomlins, Matthias D. Hofer, Kenneth Pienta, Rainer Kuefer, Robert Vessella, Xiao Wei Sun, Matthew Meyerson, Charles Lee, William R. Sellers, Arul M. Chinnaiyan, Mark A. Rubin

Research output: Contribution to journalArticle

Abstract

Prostate cancer is a common and clinically heterogeneous disease with marked variability in progression. The recent identification of gene fusions of the 5′-untranslated region of TMPRSS2 (21q22.3) with the ETS transcription factor family members, either ERG (21q22.2), ETV1 (7p21.2), or ETV4 (17q21), suggests a mechanism for overexpression of the ETS genes in the majority of prostate cancers. In the current study using fluorescence in situ hybridization (FISH), we identified the TMPRSS2:ERG rearrangements in 49.2% of 118 primary prostate cancers and 41.2% of 18 hormone-naive lymph node metastases. The FISH assay detected intronic deletions between ERG and TMPRSS2 resulting in TMPRSS2:ERG fusion in 60.3% (35 of 58) of the primary TMPRSS2:ERG prostate cancers and 42.9% (3 of 7) of the TMPRSS2:ERG hormone-naive lymph node metastases. A significant association was observed between TMPRSS2:ERG rearranged tumors through deletions and higher tumor stage and the presence of metastattc disease involving pelvic lymph nodes. Using 100K oligonucleotide single nucleotide polymorphism arrays a homogeneous deletion site between ERG and TMPRSS2 on chromosome 21q22.2-3 was identified with two distinct subclasses distinguished by the start point of the deletion at either 38.765 or 38.911 Mb. This study confirms that TMPRSS2:ERG is fused in approximately half of the prostate cancers through deletion of genomic DNA between ERG and TMPRSS2. The deletion as cause of TMPRSS2:ERG fusion is associated with clinical features for prostate cancer progression compared with tumors that lack the TMPRSS2:ERG rearrangement.

Original languageEnglish (US)
Pages (from-to)8337-8341
Number of pages5
JournalCancer Research
Volume66
Issue number17
DOIs
StatePublished - Sep 1 2006
Externally publishedYes

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Prostatic Neoplasms
Lymph Nodes
Fluorescence In Situ Hybridization
Hormones
Neoplasm Metastasis
Neoplasms
Chromosomes, Human, Pair 3
5' Untranslated Regions
Gene Fusion
Oligonucleotides
Single Nucleotide Polymorphism
Transcription Factors
DNA
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Perner, S., Demichelis, F., Beroukhim, R., Schmidt, F. H., Mosquera, J. M., Setlur, S., ... Rubin, M. A. (2006). TMPRSS2: ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. Cancer Research, 66(17), 8337-8341. https://doi.org/10.1158/0008-5472.CAN-06-1482

TMPRSS2 : ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. / Perner, Sven; Demichelis, Francesca; Beroukhim, Rameen; Schmidt, Folke H.; Mosquera, Juan Miguel; Setlur, Sunita; Tchinda, Joelle; Tomlins, Scott A.; Hofer, Matthias D.; Pienta, Kenneth; Kuefer, Rainer; Vessella, Robert; Sun, Xiao Wei; Meyerson, Matthew; Lee, Charles; Sellers, William R.; Chinnaiyan, Arul M.; Rubin, Mark A.

In: Cancer Research, Vol. 66, No. 17, 01.09.2006, p. 8337-8341.

Research output: Contribution to journalArticle

Perner, S, Demichelis, F, Beroukhim, R, Schmidt, FH, Mosquera, JM, Setlur, S, Tchinda, J, Tomlins, SA, Hofer, MD, Pienta, K, Kuefer, R, Vessella, R, Sun, XW, Meyerson, M, Lee, C, Sellers, WR, Chinnaiyan, AM & Rubin, MA 2006, 'TMPRSS2: ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer', Cancer Research, vol. 66, no. 17, pp. 8337-8341. https://doi.org/10.1158/0008-5472.CAN-06-1482
Perner S, Demichelis F, Beroukhim R, Schmidt FH, Mosquera JM, Setlur S et al. TMPRSS2: ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. Cancer Research. 2006 Sep 1;66(17):8337-8341. https://doi.org/10.1158/0008-5472.CAN-06-1482
Perner, Sven ; Demichelis, Francesca ; Beroukhim, Rameen ; Schmidt, Folke H. ; Mosquera, Juan Miguel ; Setlur, Sunita ; Tchinda, Joelle ; Tomlins, Scott A. ; Hofer, Matthias D. ; Pienta, Kenneth ; Kuefer, Rainer ; Vessella, Robert ; Sun, Xiao Wei ; Meyerson, Matthew ; Lee, Charles ; Sellers, William R. ; Chinnaiyan, Arul M. ; Rubin, Mark A. / TMPRSS2 : ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. In: Cancer Research. 2006 ; Vol. 66, No. 17. pp. 8337-8341.
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