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.
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|Titolo:||TMPRSS2:ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer.|
|Autori:||S., Perner; Demichelis, Francesca; R., Beroukhim; F. H., Schmidt; J., Mosquera; S., Setlur; J., Tchinda; S. A., Tomlins; M. D., Hofer; K. G., Pienta; R., Kuefer; R., Vessella; X., Sun; M., Meyerson; C., Lee; W. R., Sellers; A. M., Chinnaiyan; M. A., Rubin|
|Titolo del periodico:||CANCER RESEARCH|
|Anno di pubblicazione:||2006|
|Codice identificativo Scopus:||2-s2.0-33749029695|
|Codice identificativo Pubmed:||16951139|
|Codice identificativo ISI:||WOS:000240329400004|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1158/0008-5472.CAN-06-1482|
|Appare nelle tipologie:||03.1 Articolo su rivista (Journal article)|