Medulloblastoma is the most common malignant brain tumor found in childhood and represents 15% to 20% of all brain tumors and 30% to 40% of all posterior fossa tumors in this age group. Approximately 70 percent of patients are diagnosed before the age of 20 years. However, 20-25% of medulloblastomas occur in adult patients, chiefly in their third and fourth decades, and the disease is rare after the fourth decade. Children less than 3 years of age represent 25% to 35% of medulloblastoma patients. Causative factors of medulloblastoma have not been well established, however, since peak incidence occurs during childhood, factors operating very early in life might play a key role. Aside from the classic medulloblastoma, the following variants are listed in the current WHO classification: nodular/desmoplastic, extensive nodularity, large cell and anaplastic. Our current understanding of the molecular characteristic of medulloblastomas should enable a better risk stratification on the basis of immunohistochemical analysis. Gene expression profiles revealed distinct molecular subgroups of medulloblastomas, which are likely to have different cellular origins and driving mutations. At present this has permitted the identification of four to six molecular medulloblastoma subgroups. The WNT subgroup, characterized by activation of the WNT/beta-catenin signalling, shows overexpression of genes of the WNT/wingless pathway with frequent mutations of the CNNTB1 gene, loss of chromosome 6 and accumulation of nuclear b-catenin, which is considered a favorable marker. Activation of the Sonic Hedgehog (SHH) pathway characterize most desmoplastic medulloblastomas arise in a context of germline inactivating mutations in PTCH1 and SUFU, loss of 9q, and positivity for GLI1 and SFRP1. The activation of this pathway is associated with a better prognosis. Medulloblastomas that do not fall into any of these two subtypes constitute at least two other entities: one could be mainly identified by a MYCC signature (with or without MYCC amplification), whereas another might mainly be characterized by a (i)17q. The presence of MYC/MYCN amplification defines a high-risk disease.
|Title of host publication||The Medulloblastoma Book|
|Publisher||Nova Science Publishers, Inc.|
|Number of pages||13|
|ISBN (Print)||9781631171918, 9781631171901|
|Publication status||Published - Apr 1 2014|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)