ÉTUDE DES ALTÉRATIONS ÉPIGÉNÉTIQUES DES TUMEURS DES ENFANTS : LE CAS DES ÉPENDYMOMES ET DES NEUROBLASTOMES
AUTOR(ES)
Mariana Bohns Michalowski
DATA DE PUBLICAÇÃO
2006
RESUMO
During the last 10 years, a new mechanism of tumor development has been described: the hypermethylation of tumor suppressor genes. These epigenetic modifications were rarely studied in childhood cancer and large series of patients didnt exist before 2003. We studied two groups of childhood tumors; ependymoma and neuroblastome. Ependymomas (EP) represent the third most frequent type of central nervous system (CNS) tumor of childhood. No prognostic biological markers are available, and differentiation from choroid plexus papilloma (CPP) is difficult. On the other hand, neuroblastoma, the most common extracranial solid cancer diagnosed in infancy and childhood, has some genetic abnormalities that are clearly related to prognosis as NMYC amplification. Our objectives were to describe a methylation profile in these two childhood cancers and try to find a relationship between genes methylation and clinical evolution. In the first study, for a sample of 27 children with intracranial EP and 7 with CPP, we described and compared the methylation status of 19 genes. On the second study, 62 neuroblastomas were studied in terms of the methylation status of the same genes. Although we did not observe a statistical relationship between methylation and clinical outcome, the methylation pattern does not appear to be randomly distributed in ependymoma and in neuroblastoma and may represent a mechanism of tumor development and evolution. Hypermethylation was related to clinical stage in neuroblastoma: stages 1, 2 and 4s were less frequently methylated than those at stages 3 and 4 (p = 0.002). In conclusion, the results from our series indicate that hypermethylation of tumor suppressor genes may be important in the development and evolution of childhood cancers. Thus, these epigenetic alterations could be used as a marker of the disease and genes regulating methylation should be considered as possible novel therapeutic targets.
ASSUNTO(S)
hematologia pediátrica méthylation oncologia pediátrica pediatria tumeurs pédiatriques neuroblastomes gènes suppresseurs Épendymomes
ACESSO AO ARTIGO
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