Common alternative gene alterations in adult malignant astrocytomas, but not in childhood primitive neuroectodermal tumors: P16ink4 homozygous deletions and CDK4 gene amplifications

Alterations in P16ink4 or in the gene encoding one of its ligands, cyclin-dependent kinase 4 (CDK4), have been reported in human glioma cell Lines and primary tumors but not in primitive neuroectodermal tumors (PNETs), the most common malignant brain tumor of childhood. In this study the authors have examined DNA from 20 primary PNETs in children and from 20 malignant astrocytomas to assess the frequency of P16ink4 and CDK4 gene alterations associated with each type of tumor. Southern hybridization analysis revealed homozygous P16ink4 deletions in one (5%) of 20 PNETs and in seven (35%) of 20 malignant astrocytomas. The CDK4 gene amplification was evident in two additional astrocytomas, but not in any of the PNETs. In total, nine astrocytomas (45%) exhibited homozygous P16ink4 deletion or CDK4 gene amplification, but only one PNET (5%) demonstrated either gene alteration. These results indicate: that the incidence of P16ink4 and CDK4 gene alterations in these two groups of tumors is different and suggest distinct pathogenetic etiologies may be associated with each neoplasm.