title: Mutations of TP53, amplification of EGFR, MDM2 and CDK4, and deletions of CDKN2A in malignant astrocytomas.
abstract: We investigated the frequency and mutual relationship of molecular alterations in 33 malignant astrocytomas (28 glioblastomas and 5 anaplastic astrocytomas). The genetic alterations analyzed were: deletion of CDKN2a/p16 gene, TP53 mutations, and amplification of EGFR, MDM2 and CDK4. The most common genetic alteration was EGFR amplification which was revealed in 15 cases (45%). TP53 mutation was identified in 9 cases (27%) and CDKN2/p16 deletion was detected in 13 cases (41%). Either MDM2 and CDK4 amplifications were less frequent, as they were identified in 4 (12%) and 1 (3%) case, respectively. Of the 15 cases showing the amplification of EGFR, 9 had CDKN2/p16 deletion (60%, p = 0.04). On the other hand, CDKN2/p16 deletion and EGFR amplification rarely occurred with TP53 mutations (2 of 14 cases with CDKN2/p16 deletion, 14%). These results confirm the existence of at least two different pathways leading to the formation of a glioblastoma.
mesh_terms: D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D017353:Gene Deletion; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000235:genetics