Actinomycin-D treatment of high-risk ependymomas re-establishes the apoptotic function of p53

Aim of study: Ependymomas are brain tumours morphologically resembling the lining epithelium of the ventricular system of the CNS and account for 12% of all pediatric intracranial malignancies. Despite the absence of TP53 mutations, immunohistochemical accumulation of non-functional p53 is frequently observed in ependymomas and correlates with poor clinical outcome. Homozygous CDKN2A deletion is another common aberration characterizing high-risk ependymomas. Since this deletion results in excessive MDM-2 activity due to absence of p14, we believe it to comprise one important molecular mechanism of loss of p53 fu…