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Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant tumor typically appearing in childhood. Differentiation of AT/RT from other brain tumors is extremely important because of grim prognosis and necessity of more aggressive treatment. On the other hand, investigation is essential for new therapeutic agents based on continuously developing knowledge of AT/RT development mechanisms. Most AT/RT tumors have been demonstrated to harbor a chromosome 22 mutation in the region of hSNF5/INI1 gene, whose protein product participates in chromatin remodeling. Although the presence of this mutation is rather undisputable, additional molecular pathways underlying AT/RT development are poorly understood. Current paper discusses current views on molecular pathophysiology of the tumor., (© 2010 The Author(s). European Journal of Neurology © 2010 EFNS.)

A typical teratoid/rhabdoid tumor (AT/RT) is a highly malignant childhood brain tumor. Most AT/RTs are shown to contain chromosome 22 mutation in the region of hSNF5/INI1 gene, whose protein product participates in chromatin remodeling. Although the presence of this mutation is well described, molecular pathways underlying AT/RT development are poorly, if at all, understood. In the current paper we evaluate a case of AT/RT with special consideration of two pathways often implicated in tumor development: protein kinase B (PKB or Akt) and extracellular signal-regulated kinase (Erk). First, we confirmed expression of typical protein pattern being unique for AT/RT, including epithelial membrane antigen, S-100 and glial fibrillary acidic protein. In molecular analyses we tested the sample for activity of Akt and Erk kinase cascade. We found that Erk pathway signaling in the tumor was not upregulated. Neither c-Raf, MAPK nor Erk were hyperphosphorylated. On the other hand, we detected significant phosphorylation of Akt, phosphoinositide-dependent kinase-1 (PDK1) and glycogen synthase kinase 3 (GSK-3). At the same time, inhibitor of Akt pathway, phosphatase and tensin homolog (PTEN), was not upregulated. These results strongly support the hypothesis that Akt pathway contributes to chromatin remodeling disruption, promoting malignant transformation of AT/RT.