Analysis of oncogene and tumor suppressor gene alterations in pediatric malignant astrocytomas reveals reduced survival for patients with PTEN mutations

Although common among adult intracranial neoplasms, pediatric malignant ast rocytomas (PMAs) comprise a relatively small proportion of the brain tumors that occur in children, The scarcity of such cases generally requires that molecular analyses of PMAs are based on the utilization of paraffin-embedd ed material, and here we have used 39 such specimens to examine the inciden ce and prognostic significance of oncogene and tumor suppressor gene altera tions (including amplifications of EGFR, CDK4, and MDM2 as well as inactiva ting mutations of CDKN2A, TP53, and PTEN) in these tumors. In general, the frequency of alteration for the genes we have studied fell within ranges th at have been reported for adult astrocytomas, However, EGFR amplification, which is usually observed in approximately 40% and 15% of adult grade 4 and grade 3 astrocytomas, respectively, was not detected in any member of this series. With regard to prognosis, PTEN mutations were significantly associ ated with decreased survival among grade 3 and grade 4 PMA patients, a pote ntially important observation because neither patient age nor tumor maligna ncy grade was correlated with outcome for these individuals. In total, our data suggest at least one significant distinction between the genetic etiol ogy of pediatric and adult astrocytomas and additionally reveal that analys is of PTEN mutations in PMA patients may be useful in the differential diag nosis of these tumors.