Detection of TMPRSS2 : ERG fusion gene in circulating prostate cancer cells

Creative Commons Attribution-NonCommercial-Share Alike 3.0 license (CC BY-NC SA)Aim: To investigate the existence of TMPRSS2:ERG fusion gene in circulating tumor cells (CTC) from prostate cancer patients and its potential in monitoring tumor metastasis. Methods: We analyzed the frequency of TMPRSS2: ERG and TMPRSS2:ETV1 transcripts in 27 prostate cancer biopsies from prostatectomies, and TMPRSS2:ERG transcripts in CTC isolated from 15 patients with advanced androgen independent disease using reverse transcription polymerase chain reaction (RT-PCR). Fluorescence in situ hybridization (FISH) was applied to analyze the genomic truncation of ERG, which is the result of TMPRSS2:ERG fusion in 10 of the 15 CTC samples. Results: TMPRSS2: ERG transcripts were found in 44% of our samples, but we did not detect expression of TMPRSS2:ETV1. Using FISH analysis we detected chromosomal rearrangements affecting the ERG gene in 6 of 10 CTC samples, including 1 case with associated TMPRSS2:ERG fusion at the primary site. However, TMPRSS2:ERG transcripts were not detected in any of the 15 CTC samples, including the 10 cases analyzed by FISH. Conclusion: Although further study is required to address the association between TMPRSS2:ERG fusion and prostate cancer metastasis, detection of genomic truncation of the ERG gene by FISH analysis could be useful for monitoring the appearance of CTC and the potential for prostate cancer metastasis.Peer reviewedFinal Published versio

Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer

Background: The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer. Methods: In this study, fluorescent in situ hybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of four ERG and one TMPRSS2 SNPs using germline DNA was also performed in a sample of the cases (n = 127). Results: Of the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5% were negative and 35.5% were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95% CI = 0.22-3.93), nor was there a significant difference in causespecific survival when stratifying by translocation or deletion (HR = 0.84, 95% CI = 0.23-3.12) or by the number of retained fusion copies (HR = 1.22, 95% CI = .45-3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of the TMPRSS2 SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03). Conclusion: If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer.This work was supported by NIH grants RO1 CA56678, RO1 CA114524, and P50 CA97186; additional support was provided by the Fred Hutchinson Cancer Research Center and the Intramural Program of the National Human Genome Research Institute

Clear cell hidradenoma of the skin - a third tumor type with a t(11;19)-associated TORC1-MAML2 gene fusion

Recent studies have shown that the t(11;19)(q21;p13) translocation in mucoepidermoid carcinomas and benign Warthin's tumors results in a fusion of the N-terminal CREB-binding domain of the cAMP coactivator TORCI (a.k.a. MECT1 and WAMTP1) to the Notch coactivator MAML2. Here we show that a third tumor type, clear cell hidradenoma of the skin, also expresses this gene fusion. RT-PCR analysis of a clear cell hidradenoma with at(11;19)(q21;p13) translocation revealed expression of a TORC1-MAML2 fusion transcript consisting of exon 1 of TORC1 fused to exons 2-5 of MAML2. Because the fusion was only detected in a single case, the frequency of this aberration in clear cell hidradenomas remains unknown. These results demonstrate that the t(11; 19) in mucoepidermoid carcinoma, Warthin's tumor, and clear cell hidradenoma targets the same genes and results in identical gene fusions, indicating that at least subgroups of these glandular tumors evolve through activation of the same molecular pathways

[Une approche de la recherche publique au travers de ses collectifs de recherche : une vue d'ensemble]

Le but principal de ce rapport est d'établir une comparaison internationale de la recherche publique dans les pays de l'Union européenne (et, plus largement, ceux de l'OCDE). Un deuxième volet propose une approche basée sur l'analyse des collectifs de recherche, afin de développer une méthodologie cohérente pour établir des analyses comparées par pays d'un secteur vital à la sécurité et au bien-être publics. Ce rapport est basé sur un travail qui a montré que l'activité de recherche est une préoccupation collective et que, en utilisant une image provocante, les unités de recherche ou les laboratoires sont à la science ce que les entreprises sont à l'économie : l'unité de production de base