TMPRSS2
MIM.602060 21q22.3
Prostate cancer
TMPRSS2 gene fusions with ETS transcription factor family members ERG, ETV1, or ETV4 have been recently discovered as a common molecular event in prostate cancer.
Although several studies have been done, the clinical utility of TMPRSS2 genetic alterations as biomarkers for prostate carcinoma remains indeterminate.
No normal prostate samples show TMPRSS2 translocation or deletion.
Sixty-two percent (62%) patients of prostate carcinomas demonstrate TMPRSS2 gene alterations, including 39% with translocation, 16% with deletion, and 7% with a mixed pattern.
Tissue heterogeneity for TMPRSS2 gene alterations is identified in 28% of prostate carcinomas.
No difference in the frequency of TMPRSS2 gene alterations is found between Gleason 6 and 7 tumors.
70% of prostatic intraepithelial neoplasia (PIN) have TMPRSS2 gene alterations and show the same FISH patterns as in the carcinomas from respective prostatectomy specimens.
The TMPRSS2 dual-color break-apart FISH probe cocktail provides a simple and reliable method for the detection of TMPRSS2-related genetic alterations in formalin-fixed paraffin-embedded tissue.
TMPRSS2 genetic alterations detectable by this method are strictly restricted in prostate neoplasia, and can be identified in the majority of prostate carcinomas.
Tissue heterogeneity for TMPRSS2 alterations is common, and it should be considered when sampling and evaluating biopsy specimens.
Pathology
gene fusions of the 5’-untranslated region of TMPRSS2 (21q22.3) with the ETS transcription factor family members in prostate cancer (prostatic adenocarcinomas) :
- ERG (21q22.2) : TMPRSS2:ERG (#17584912#)
- ETV1 (7p21.2) TMPRSS2:ETV1 (#16254181#)
- ETV4 (17q21) TMPRSS2:ETV4 (#16951139#)
References
Detection of TMPRSS2 gene deletions and translocations in carcinoma, intraepithelial neoplasia, and normal epithelium of the prostate by direct fluorescence in situ hybridization. Zhang S, Pavlovitz B, Tull J, Wang Y, Deng FM, Fuller C. Diagn Mol Pathol. 2010 Sep;19(3):151-6. PMID: #20736744#
Tu JJ, Rohan S, Kao J, Kitabayashi N, Mathew S, Chen YT. Gene fusions between TMPRSS2 and ETS family genes in prostate cancer: frequency and transcript variant analysis by RT-PCR and FISH on paraffin-embedded tissues. Mod Pathol. 2007 Jul 13; PMID: #17632455#
Winnes M, Lissbrant E, Damber JE, Stenman G. Molecular genetic analyses of the TMPRSS2-ERG and TMPRSS2-ETV1 gene fusions in 50 cases of prostate cancer. Oncol Rep. 2007 May;17(5):1033-6. PMID: #17390040#
Mehra R, Tomlins SA, Shen R, Nadeem O, Wang L, Wei JT, Pienta KJ, Ghosh D, Rubin MA, Chinnaiyan AM, Shah RB. Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer. Mod Pathol. 2007 May;20(5):538-44. Epub 2007 Mar 2. PMID: #17334343#
Laxman B, Tomlins SA, Mehra R, Morris DS, Wang L, Helgeson BE, Shah RB, Rubin MA, Wei JT, Chinnaiyan AM. Noninvasive detection of TMPRSS2:ERG fusion transcripts in the urine of men with prostate cancer. Neoplasia. 2006 Oct;8(10):885-8. PMID: #17059688#
Perner S, Demichelis F, Beroukhim R, Schmidt FH, Mosquera JM, Setlur S, Tchinda J, Tomlins SA, Hofer MD, Pienta KG, Kuefer R, Vessella R, Sun XW, Meyerson M, Lee C, Sellers WR, Chinnaiyan AM, Rubin MA. TMPRSS2:ERG Fusion-Associated Deletions Provide Insight into the Heterogeneity of Prostate Cancer. Cancer Res. 2006 Sep 1;66(17):8337-41. PMID: #16951139#
Tomlins SA, Mehra R, Rhodes DR, Smith LR, Roulston D, Helgeson BE, Cao X, Wei JT, Rubin MA, Shah RB, Chinnaiyan AM. TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer. Cancer Res. 2006 Apr 1;66(7):3396-400. PMID: #16585160#
Yoshimoto M, Ludkovski O, Bayani J, Graham C, Zielenska M, Squire JA. Microdeletion and concurrent translocation associated with a complex TMPRSS2:ERG prostate cancer gene fusion. Genes Chromosomes Cancer. 2007 Jun 21; PMID: #17584912#
Perner S, Demichelis F, Beroukhim R, Schmidt FH, Mosquera JM, Setlur S, Tchinda J, Tomlins SA, Hofer MD, Pienta KG, Kuefer R, Vessella R, Sun XW, Meyerson M, Lee C, Sellers WR, Chinnaiyan AM, Rubin MA. TMPRSS2:ERG Fusion-Associated Deletions Provide Insight into the Heterogeneity of Prostate Cancer. Cancer Res. 2006 Sep 1;66(17):8337-41. PMID: #16951139#
Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, Varambally S, Cao X, Tchinda J, Kuefer R, Lee C, Montie JE, Shah RB, Pienta KJ, Rubin MA, Chinnaiyan AM. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005 Oct 28;310(5748):644-8. PMID: #16254181#