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Inicio Actas Urológicas Españolas (English Edition) Prostate cancer: The revolution of the fusion genes
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Vol. 35. Issue 7.
Pages 420-428 (July - August 2011)
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Vol. 35. Issue 7.
Pages 420-428 (July - August 2011)
Review article
Prostate cancer: The revolution of the fusion genes
Cáncer de próstata: la revolución de los genes de fusión
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2105
A. Fernández-Serraa, J. Rubio-Brionesb, Z. García-Casadoa, E. Solsonab, J.A. López-Guerreroa,
Corresponding author
jalopez@fivo.org

Corresponding author.
a Laboratorio de Biología Molecular, Fundación Instituto Valenciano de Oncología, Valencia, Spain
b Servicio de Urología, Fundación Instituto Valenciano de Oncología, Valencia, Spain
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Tables (2)
Table 1. Gene fusions described in CP that do not involve TMPRSS2 or ERG and are in the minority in terms of incidence, although of great interest in the elucidation of molecular mechanisms involved in the CP.
Table 2. Prognostic implications of the presence of TMPRSS2-ETS or features related with the gene.
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Abstract
Background

TMPRSS2-ETS fusion gene rearrangements constitute a very common and specific alteration in prostate cancer cells. These genetic alterations lead the overexpression of ETS genes which encode the E26 family of transcription factors involved in cell proliferation. Of this family, the ERG oncogene is overexpressed in almost 50% of prostate cancer cases.

Evidence synthesis

TMPRSS2-ERG overexpresses ERG through an androgen-mediated response. Structurally, the rearrangement is due to interstitial deletion and to a lesser extent to reciprocal translocation and plays a key role in cellular metabolism. Almost all fusion gene transcripts produce a truncated ERG protein and the presence of a specific isoform of this gene suggests the clonality of the tumor; hence, metastasis shares the fusion gene status of their primary lesion. Although the prognostic implications of TMPRSS2-ERG have not been fully elucidated, they constitute a field of great diagnostic potential and, therefore, the development of techniques to identify and to analyze the presence and characteristics of this gene in a non-invasive fashion deserves great interest in this area. Currently, there is evidence supporting the hypothesis that the presence of fusion gene differentiates two molecular groups within prostate cancer with a differential behavior making the fusion gene a potential therapeutic target. In this regard, the use of anti-HDAC (trichostatin), antagonists of estrogen receptor alpha and abiraterone acetate have shown promising results.

Conclusions

This review describes the great potential offered by the investigation of fusion genes in PC and the need for further studies.

Keywords:
TMPRSS2-ERG
Prostate cancer
Prognostic
Diagnostic
Fusion genes
Resumen
Contexto

Los reordenamientos TMPRSS2-ETS constituyen una alteración específica y frecuente en tumores prostáticos que conlleva la sobreexpresión de los genes ETS que codifican para la familia E26 de factores de transcripción, promoviendo la proliferación celular. De entre estos ERG sobreexpresa en casi el 50% de los carcinomas prostáticos.

Síntesis de evidencia

TMPRSS2-ERG sobreexpresa a ERG en respuesta a andrógenos. Estructuralmente este reordenamiento se debe a una deleción intersticial y, en menor medida, a una translocación recíproca, y tiene un papel clave en el metabolismo celular. Casi todos los transcritos del gen de fusión producen una proteína ERG truncada, y la presencia de una determinada isoforma de este gen indica la clonalidad del tumor, de modo que la metástasis comparte isoforma de TMPRSS2-ERG con su localización primaria. Aunque las implicaciones pronósticas de TMPRSS2-ERG no están totalmente elucidadas se considera un campo de gran potencial diagnóstico, por lo que el desarrollo de técnicas que permitan determinar la presencia y características de este gen de forma no invasiva es muy interesante. La presencia del gen de fusión constituye dos grupos moleculares dentro del CaP con un comportamiento evolutivo claramente diferencial, lo que hace que farmacológicamente el gen de fusión constituya una diana terapéutica potencial. En este sentido, el uso de fármacos anti-HDAC (tricostatina), antagonistas del receptor de estrógenos alfa y acetato de abiraterona han mostrado resultados prometedores.

Conclusiones

Esta revisión expone el gran potencial que representa la investigación de los genes de fusión en el CaP y la necesidad de profundizar en su estudio.

Palabras clave:
TMPRSS2-ERG
Cáncer de próstata
Pronóstico
Diagnóstico
Genes de fusión

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