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

TitleTMPRSS2:ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer.
Publication TypeJournal Article
Year of Publication2006
AuthorsPerner S, Demichelis F, Beroukhim R, Schmidt FH, Mosquera J-M, Setlur S, Tchinda J, Tomlins SA, Hofer MD, Pienta KG, Kuefer R, Vessella R, Sun X-W, Meyerson M, Lee C, Sellers WR, Chinnaiyan AM, Rubin MA
JournalCancer Res
Date Published2006 Sep 1
Keywords5' Untranslated Regions, Cell Line, Tumor, Gene Deletion, Humans, Male, Oncogene Proteins, Fusion, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Transcription, Genetic

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 metastatic 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.

Alternate JournalCancer Res.
PubMed ID16951139
Grant ListP50 CA090381 / CA / NCI NIH HHS / United States
P50 CA097186 / CA / NCI NIH HHS / United States
P50 CA69568 / CA / NCI NIH HHS / United States
R01AG21404 / AG / NIA NIH HHS / United States
R01CA109038 / CA / NCI NIH HHS / United States
T32 CA009172 / CA / NCI NIH HHS / United States