[TMPRSS2-ETS gene fusion in prostate cancer].
BACKGROUND
Recurrent chromosomal rearrangements have not been well characterized in common carcinomas. Using a novel bioinformatics approach, our group recently described a novel gene fusion in PCa. This fusion involves the androgen-regulated gene TMPRSS2 and so far three members of the ETS family of transcription factors already described as rearranged in the Ewing's family of tumors. By analogy, fusion status in prostate cancer may determine clinical outcome and secondary genetic alterations as witnessed in Ewing's tumors.


METHODS
These novel gene fusions occur in the majority of prostate cancers identified by PSA screening and are the driving mechanism for overexpression of the three members of the ETS transcription factor family, either ERG (21q22.3), ETV1 (7p21.2), or ETV4 (17q21). Considering the high incidence of prostate cancer and the high frequency of this gene fusion, the TMPRSS2-ETS gene fusion is the most common genetic aberration so far described in human malignancies.


RESULTS
So far, this is the only gene rearrangement in any of the most prevalent cancers. As confirmed by other groups, we demonstrated that, within the group of ETS transcription factors, ERG is the most common fusion partner of the ETS genes with TMPRSS2. This gene fusion is considered to be an early event in PCa development. Emerging data suggest that gene fusion PCa demonstrates a distinct clinical course and thus support its use as a diagnostic test and prognostic biomarker. Also similar to the Philadelphia chromosome in chronic myelogenous leukemia (CML), the gene fusion in prostate cancer has potential as an important candidate for the development of targeted therapy.
Perner
S
S
Department of Pathology, Brigham & Women's Hospital/Harvard Medical School, 221 Longwood Avenue, EBRC 442A, Boston, MA 02115-6110, USA.
Schmidt
F H
FH
Hofer
M D
MD
Kuefer
R
R
Rubin
M
M
D014408:Biomarkers, Tumor / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D050596:Oncogene Fusion / Q000235:genetics*; D015995:Prevalence; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D050783:Proto-Oncogene Proteins c-ets; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human