Mutations of TP53, Amplification of EGFR, MDM2 and CDK4, and Deletions of CDKN2A in Malignant Astrocytomas*

Laboratories of Tumor Biology, Chair of Oncology, Lodz

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.

Address for correspondence and reprint requests to:
W. Biernat M. D.,
Chair of Oncology,
Paderewski 4, 93-509 Lodz.

* This project is supported by the National Research Committee (KBN) grant.