title: Hypermethylation of apoptotic genes as independent prognostic factor in neuroblastoma disease.
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.
authors.affiliation: Unidad de Genética y Diagnóstico Prenatal, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Grau
authors.forename: Francisco
authors.initials: F
authors.lastname: Martinez
authors.forename: Carmen
authors.initials: C
authors.lastname: Orellana
authors.forename: Adela
authors.initials: A
authors.lastname: Canete
authors.forename: Yania
authors.initials: Y
authors.lastname: Yañez
authors.forename: Silvestre
authors.initials: S
authors.lastname: Oltra
authors.forename: Rosa
authors.initials: R
authors.lastname: Noguera
authors.forename: Miguel
authors.initials: M
authors.lastname: Hernandez
authors.forename: Jose D
authors.initials: JD
authors.lastname: Bermúdez
authors.forename: Victoria
authors.initials: V
authors.lastname: Castel
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics*; D053468:CARD Signaling Adaptor Proteins; D053181:Caspase 8 / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; C402202:PYCARD protein, human; C505530:CASP8 protein, human; D053181:Caspase 8