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Theses

ETUDE DES ALTÉRATIONS EPIGENETIQUES DES TUMEURS DES
ENFANTS : LE CAS DES ÉPENDYMOMES ET DES NEUROBLASTOMES

Abstract : 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 didn't 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.
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https://tel.archives-ouvertes.fr/tel-00115184
Contributor : Mariana Michalowski <>
Submitted on : Monday, November 20, 2006 - 3:33:33 PM
Last modification on : Friday, November 6, 2020 - 4:11:53 AM
Long-term archiving on: : Tuesday, April 6, 2010 - 7:45:36 PM

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  • HAL Id : tel-00115184, version 1

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Mariana Michalowski. ETUDE DES ALTÉRATIONS EPIGENETIQUES DES TUMEURS DES
ENFANTS : LE CAS DES ÉPENDYMOMES ET DES NEUROBLASTOMES. Ingénierie biomédicale. Université Joseph-Fourier - Grenoble I, 2006. Français. ⟨tel-00115184⟩

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