PMID- 22081504 OWN - NLM STAT- MEDLINE DCOM- 20120904 LR - 20201209 IS - 1098-2264 (Electronic) IS - 1045-2257 (Linking) VI - 51 IP - 3 DP - 2012 Mar TI - FLI1 is a novel ETS transcription factor involved in gene fusions in prostate cancer. PG - 240-9 LID - 10.1002/gcc.20948 [doi] AB - To characterize the pattern of ETS rearrangements and to uncover novel ETS fusion genes, we analyzed 200 prostate carcinomas (PCa) with TaqMan low-density arrays (TLDAs), followed by selective analyses with fluorescence in situ hybridization (FISH), RT-PCR, and sequencing. Besides confirming the recurrent presence of ERG, ETV1, ETV4, and ETV5 rearrangements, we here report FLI1 as the fifth ETS transcription factor involved in fusion genes in prostate cancer. Outlier expression of the FLI1 gene was detected by TLDAs in one PCa that showed relative overexpression of FLI1 exons 4:5 as compared with FLI1 exons 2:3. A structural rearrangement was found using FISH probes flanking the FLI1 gene and RT-PCR and sequencing analyses showed fusion of SLC45A3 exon 1 with FLI1 exon 3. Interestingly, we found four cases with two different ETS rearrangements in the index tumor, thus revealing intratumor genetic heterogeneity. Correlation analysis with clinico-pathological data showed association of ERG rearrangements with locally advanced disease (pT3, P = 0.007) and MYC overexpression (P = 0.001), and association of ETV1 rearrangements with PTEN downregulation (P = 0.015). We report that FLI1 is a novel ETS transcription factor involved in gene fusions in prostate cancer and that intratumor genetic heterogeneity of ETS rearrangements can occasionally be found in index primary tumors. CI - Copyright (c) 2011 Wiley Periodicals, Inc. FAU - Paulo, Paula AU - Paulo P AD - Department of Genetics, Portuguese Oncology Institute, Porto, Portugal. FAU - Barros-Silva, Joao D AU - Barros-Silva JD FAU - Ribeiro, Franclim R AU - Ribeiro FR FAU - Ramalho-Carvalho, Joao AU - Ramalho-Carvalho J FAU - Jeronimo, Carmen AU - Jeronimo C FAU - Henrique, Rui AU - Henrique R FAU - Lind, Guro E AU - Lind GE FAU - Skotheim, Rolf I AU - Skotheim RI FAU - Lothe, Ragnhild A AU - Lothe RA FAU - Teixeira, Manuel R AU - Teixeira MR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111112 PL - United States TA - Genes Chromosomes Cancer JT - Genes, chromosomes & cancer JID - 9007329 RN - 0 (DNA-Binding Proteins) RN - 0 (ERG protein, human) RN - 0 (ETV1 protein, human) RN - 0 (FLI1 protein, human) RN - 0 (Membrane Transport Proteins) RN - 0 (Monosaccharide Transport Proteins) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (Proto-Oncogene Protein c-fli-1) RN - 0 (SLC45a3 protein, human) RN - 0 (Trans-Activators) RN - 0 (Transcription Factors) RN - 0 (Transcriptional Regulator ERG) SB - IM MH - Adenocarcinoma/*genetics/pathology MH - Aged MH - Base Sequence MH - DNA-Binding Proteins/genetics MH - Exons MH - Gene Rearrangement MH - Genetic Heterogeneity MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Membrane Transport Proteins/*genetics MH - Middle Aged MH - Molecular Sequence Data MH - Monosaccharide Transport Proteins MH - Neoplasm Staging MH - Oligonucleotide Array Sequence Analysis MH - *Oncogene Fusion MH - Oncogene Proteins, Fusion/*genetics MH - Prostatic Neoplasms/*genetics/pathology MH - Proto-Oncogene Protein c-fli-1/*genetics MH - Trans-Activators/genetics MH - Transcription Factors/genetics MH - Transcriptional Regulator ERG EDAT- 2011/11/15 06:00 MHDA- 2012/09/05 06:00 CRDT- 2011/11/15 06:00 PHST- 2011/07/17 00:00 [received] PHST- 2011/10/10 00:00 [accepted] PHST- 2011/11/15 06:00 [entrez] PHST- 2011/11/15 06:00 [pubmed] PHST- 2012/09/05 06:00 [medline] AID - 10.1002/gcc.20948 [doi] PST - ppublish SO - Genes Chromosomes Cancer. 2012 Mar;51(3):240-9. doi: 10.1002/gcc.20948. Epub 2011 Nov 12.