PMID- 16951139 OWN - NLM STAT- MEDLINE DCOM- 20071126 LR - 20220331 IS - 1538-7445 (Electronic) IS - 0008-5472 (Linking) VI - 66 IP - 17 DP - 2006 Sep 1 TI - TMPRSS2:ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. PG - 8337-41 AB - 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. FAU - Perner, Sven AU - Perner S AD - Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, EBRC 442A, 221 Longwood Avenue, Boston, MA 02115-6110, USA. FAU - Demichelis, Francesca AU - Demichelis F FAU - Beroukhim, Rameen AU - Beroukhim R FAU - Schmidt, Folke H AU - Schmidt FH FAU - Mosquera, Juan-Miguel AU - Mosquera JM FAU - Setlur, Sunita AU - Setlur S FAU - Tchinda, Joelle AU - Tchinda J FAU - Tomlins, Scott A AU - Tomlins SA FAU - Hofer, Matthias D AU - Hofer MD FAU - Pienta, Kenneth G AU - Pienta KG FAU - Kuefer, Rainer AU - Kuefer R FAU - Vessella, Robert AU - Vessella R FAU - Sun, Xiao-Wei AU - Sun XW FAU - Meyerson, Matthew AU - Meyerson M FAU - Lee, Charles AU - Lee C FAU - Sellers, William R AU - Sellers WR FAU - Chinnaiyan, Arul M AU - Chinnaiyan AM FAU - Rubin, Mark A AU - Rubin MA LA - eng GR - R01AG21404/AG/NIA NIH HHS/United States GR - R01CA109038/CA/NCI NIH HHS/United States GR - T32 CA009172/CA/NCI NIH HHS/United States GR - P50 CA69568/CA/NCI NIH HHS/United States GR - P50 CA097186/CA/NCI NIH HHS/United States GR - P50 CA090381/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (5' Untranslated Regions) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (TMPRSS2-ERG fusion protein, human) SB - IM MH - 5' Untranslated Regions MH - Cell Line, Tumor MH - *Gene Deletion MH - Humans MH - Male MH - Oncogene Proteins, Fusion/*genetics MH - Polymerase Chain Reaction MH - Polymorphism, Single Nucleotide MH - Prostatic Neoplasms/*genetics MH - Transcription, Genetic EDAT- 2006/09/05 09:00 MHDA- 2007/12/06 09:00 CRDT- 2006/09/05 09:00 PHST- 2006/09/05 09:00 [pubmed] PHST- 2007/12/06 09:00 [medline] PHST- 2006/09/05 09:00 [entrez] AID - 66/17/8337 [pii] AID - 10.1158/0008-5472.CAN-06-1482 [doi] PST - ppublish SO - Cancer Res. 2006 Sep 1;66(17):8337-41. doi: 10.1158/0008-5472.CAN-06-1482.