Hypermethylation of apoptotic genes as independent prognostic factor in neuroblastoma disease.

Autores de IIS La Fe

• Elena Grau García

  Autor

• 

  Francisco Martínez Castellano

  Autor

• Carmen Orellana Alonso

  Autor

• Adela Cañete Nieto

  Autor

• Yania Yañez Peralta

  Autor

• Juan Silvestre Oltra Soler

  Autor

• Rosa Noguera Salvá

  Autor

• Miguel Jose Hernandez Marti

  Autor

• Jose Domingo Bermudez Edo

  Autor

• Victoria Castel Sánchez

  Autor

Grupos

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  Biomedicina Molecular, Celular y Genómica

• Investigación Clínica y Traslacional en Cáncer

• Investigación Traslacional en Genética

• Reumatología

Abstract

Neuroblastoma (NB) is an embryonal tumour of neuroectodermal cells, and its prognosis is based on patient age at diagnosis, tumour stage and MYCN amplification, but it can also be classified according to their degree of methylation. Considering that epigenetic aberrations could influence patient survival, we studied the methylation status of a series of 17 genes functionally involved in different cellular pathways in patients with NB and their impact on survival. We studied 82 primary NB tumours and we used methylation-specific-PCR to perform the epigenetic analysis. We evaluated the putative association among the evidence of hypermethylation with the most important NB prognostic factors, as well as to determine the relationship among methylation, clinical classification and survival. CASP8 hypermethylation showed association with relapse susceptibility and, TMS1 and APAF1 hypermethylation are associated with bad prognosis and showed high influence on NB overall survival. Hypermethylation of apoptotic genes has been identified as a good candidate of prognostic factor. We propose the simultaneous analysis of hypermethylation of APAF1, TMS1 and CASP8 apoptotic genes on primary NB tumour as a good prognostic factor of disease progression.