ABSENCE OF P53 GENE-MUTATIONS IN A TUMOR PANEL REPRESENTATIVE OF PILOCYTIC ASTROCYTOMA DIVERSITY USING A P53 FUNCTIONAL ASSAY

Although p53-gene mutations occur with significant frequency in diffus e low-grade and high-grade astrocytomas, and are postulated to play an important role in tumorigenesis in these cases, the role of the p53 g ene in pilocytic astrocytomas remains unclear. Published data using DN A-based assays for p53-gene analysis in these tumors have shown contra dictory results in mutation frequency (0-14%). It is not known whether these heterogeneous results seem from the biological diversity of thi s tumor group or from technical problems. To re-evaluate p53-gene stat us in pilocytic tumors, we analyzed 18 tumors chosen to represent the clinical and biological heterogeneity of this tumor type with respect to anatomical location, patient age, gender, ethnic origin (Caucasian or Japanese) and the concomitant occurrence of neurofibromatosis type 1 (NF1). All primary tumors were histologically diagnosed as pilocytic astrocytoma (WHO grade I), except for one anaplastic pilocytic astroc ytoma (WHO grade III) which developed in an NF1 patient and recurred a s glioblastoma multiforme (WHO grade IV). p53 mutations were detected using an assay in yeast which tests the transcriptional activity of p5 3 proteins synthesized from tumor mRNA-derived p53-cDNA templates. Non e of 18 tumors, including 3 NF1-related tumors, showed p53-gene mutati ons between and including exons 4 and 11. We conclude that p53-gene mu tations ave extremely rare findings in pilocytic astrocytomas, and are absent even in those exceptional Eases in which malignant progression of such tumors has occurred. (C) 1998 Wiley-Liss, Inc.