PMID- 18794152 OWN - NLM STAT- MEDLINE DCOM- 20081014 LR - 20211020 IS - 1538-7445 (Electronic) IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 68 IP - 18 DP - 2008 Sep 15 TI - A fluorescence in situ hybridization screen for E26 transformation-specific aberrations: identification of DDX5-ETV4 fusion protein in prostate cancer. PG - 7629-37 LID - 10.1158/0008-5472.CAN-08-2014 [doi] AB - Recurrent gene fusions involving E26 transformation-specific (ETS) transcription factors ERG, ETV1, ETV4, or ETV5 have been identified in 40% to 70% of prostate cancers. Here, we used a comprehensive fluorescence in situ hybridization (FISH) split probe strategy interrogating all 27 ETS family members and their five known 5' fusion partners in a cohort of 110 clinically localized prostate cancer patients. Gene rearrangements were only identified in ETS genes that were previously implicated in prostate cancer gene fusions including ERG, ETV1, and ETV4 (43%, 5%, and 5%, respectively), suggesting that a substantial fraction of prostate cancers (estimated at 30-60%) cannot be attributed to an ETS gene fusion. Among the known 5' gene fusion partners, TMPRSS2 was rearranged in 47% of cases followed by SLC45A3, HNRPA2B1, and C15ORF21 in 2%, 1%, and 1% of cases, respectively. Based on this comprehensive FISH screen, we have made four noteworthy observations. First, by screening the entire ETS transcription factor family for rearrangements, we found that a large fraction of prostate cancers (44%) cannot be ascribed to an ETS gene fusion, an observation which will stimulate research into identifying recurrent non-ETS aberrations in prostate cancers. Second, we identified SLC45A3 as a novel 5' fusion partner of ERG; previously, TMPRSS2 was the only described 5' partner of ERG. Third, we identified two prostate-specific, androgen-induced genes, FLJ35294 and CANT1, as 5' partners to ETV1 and ETV4. Fourth, we identified a ubiquitously expressed, androgen-insensitive gene, DDX5, fused in frame with ETV4, leading to the expression of a DDX5-ETV4 fusion protein. FAU - Han, Bo AU - Han B AD - Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. FAU - Mehra, Rohit AU - Mehra R FAU - Dhanasekaran, Saravana M AU - Dhanasekaran SM FAU - Yu, Jindan AU - Yu J FAU - Menon, Anjana AU - Menon A FAU - Lonigro, Robert J AU - Lonigro RJ FAU - Wang, Xiaosong AU - Wang X FAU - Gong, Yusong AU - Gong Y FAU - Wang, Lei AU - Wang L FAU - Shankar, Sunita AU - Shankar S FAU - Laxman, Bharathi AU - Laxman B FAU - Shah, Rajal B AU - Shah RB FAU - Varambally, Sooryanarayana AU - Varambally S FAU - Palanisamy, Nallasivam AU - Palanisamy N FAU - Tomlins, Scott A AU - Tomlins SA FAU - Kumar-Sinha, Chandan AU - Kumar-Sinha C FAU - Chinnaiyan, Arul M AU - Chinnaiyan AM LA - eng SI - GENBANK/EU693077 SI - GENBANK/EU693078 SI - GENBANK/EU693079 SI - GENBANK/FLJ35294 GR - P50 CA069568-110020/CA/NCI NIH HHS/United States GR - R01 CA102872/CA/NCI NIH HHS/United States GR - P50CA69568/CA/NCI NIH HHS/United States GR - R01 CA097063-01/CA/NCI NIH HHS/United States GR - P50 CA069568/CA/NCI NIH HHS/United States GR - U01 CA111275/CA/NCI NIH HHS/United States GR - R01 CA097063/CA/NCI NIH HHS/United States GR - HHMI/Howard Hughes Medical Institute/United States GR - U01 CA111275-01/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 (Adenovirus E1A Proteins) RN - 0 (ETV4 protein, human) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Proto-Oncogene Proteins c-ets) RN - 0 (Transcription Factors) RN - EC 3.6.1.- (Ddx5 protein, human) RN - EC 3.6.4.13 (DEAD-box RNA Helicases) SB - IM MH - Adenovirus E1A Proteins/*genetics MH - Base Sequence MH - Cell Line, Tumor MH - Cell Transformation, Neoplastic/*genetics MH - DEAD-box RNA Helicases/*genetics MH - Gene Rearrangement MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Molecular Sequence Data MH - Oncogene Proteins, Fusion/*genetics MH - Prostatic Neoplasms/*genetics MH - Proto-Oncogene Proteins/*genetics MH - Proto-Oncogene Proteins c-ets MH - Transcription Factors/genetics PMC - PMC2760292 MID - NIHMS134703 EDAT- 2008/09/17 09:00 MHDA- 2008/10/15 09:00 PMCR- 2009/10/12 CRDT- 2008/09/17 09:00 PHST- 2008/09/17 09:00 [pubmed] PHST- 2008/10/15 09:00 [medline] PHST- 2008/09/17 09:00 [entrez] PHST- 2009/10/12 00:00 [pmc-release] AID - 68/18/7629 [pii] AID - 10.1158/0008-5472.CAN-08-2014 [doi] PST - ppublish SO - Cancer Res. 2008 Sep 15;68(18):7629-37. doi: 10.1158/0008-5472.CAN-08-2014.