Words similar to medulloblastomas
Example sentences for: medulloblastomas
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The greatly increased incidence of medulloblastomas in patients inheriting mutations in the APC tumor suppressor gene suggests that activation of Wnt signaling could be sufficient in some cases to initiate medulloblastoma formation.
Strain effects are unlikely to have played a role in this lack of a neoplastic phenotype, as mice with the same background as the one we used have previously been shown to develop medulloblastomas [ 12 ] . We further attempted to induce CNS tumors by abrogating p53 function in conjunction with transgenic β-catenin expression.
Affected individuals develop a large spectrum of CNS and extra-CNS neoplasms, including medulloblastomas [ 2 ] . Interestingly, alterations in p53 are relatively rare in sporadic medulloblastomas, with mutations detected in 5% or less of cases [ 3 4 ] .
Mutations in the Hedgehog pathway members PTCH , PTCH 2 , SUFU and Smo , have all been identified in sporadic medulloblastomas as well, with approximately 25% of cases containing mutations affecting these genes [ 5 6 7 8 9 ] . A murine medulloblastoma model was recently developed by disruption of the PTCH gene, with medulloblastoma-like tumors arising in 10-15% of heterozygotes by 9 months of age [ 10 11 ] . Breeding PTCH mice to p53 knockout animals markedly increased tumor incidence.
APC mutations have been identified in medulloblastoma cell lines and up to 4% of sporadic medulloblastomas [ 16 17 ] . Furthermore, point mutations or small deletions in β- catenin exon 3 have been identified in 5-10% of sporadic medulloblastomas and in supratentorial primitive neuroectodermal tumors (PNETs) [ 17 18 19 ] . Finally, large deletions in AXIN were recently found in 12% of sporadic medulloblastomas [ 20 ] . In the absence of Wnt signaling β-catenin is sequestered in the cytoplasm, and nuclear translocation of β-catenin has been used to monitor activation of the Wnt pathway in a number of different tumor types.
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