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FLI1 is a novel ETS transcription factor involved in gene fusions in prostate cancer
Author(s) -
Paulo Paula,
BarrosSilva João D.,
Ribeiro Franclim R.,
RamalhoCarvalho João,
Jerónimo Carmen,
Henrique Rui,
Lind Guro E.,
Skotheim Rolf I.,
Lothe Ragnhild A.,
Teixeira Manuel R.
Publication year - 2012
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20948
Subject(s) - ets transcription factor family , fusion gene , biology , fli1 , exon , ets1 , prostate cancer , gene , transcription factor , cancer research , tmprss2 , pten , genetics , microbiology and biotechnology , cancer , medicine , pathology , disease , apoptosis , covid-19 , pi3k/akt/mtor pathway , infectious disease (medical specialty)
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. © 2011 Wiley Periodicals, Inc.