P53 mutation, EGFR gene amplification and loss of heterozygosity on chromosome 10, 17 p in human gliomas

Objective To further illustrate the roles of p53 gene, epidermal growth fac tor receptor (EGFR) gene and loss of heterozygosity (LOH) on chromosome 10 and 17 p in human glioma progression. Methods p53 mutations were scanned in 50 gliomas with various malignant gra des using the polymerase chain reaction single strand conformation polymorp hism (PCR-SSCP) assay, and were confirmed by direct sequencing. LOH for chr omosome 10, 17p and amplification of the EGFR gene were also assessed using Southern blot analysis. Results p53 mutations were found in 9 of 17 high-grade astrocytomas (53%), 1 of 15 low-grade astrocytomas (7%), and the only subject of eppenctymoblas toma but in none of the 10 medulloblastomas and 7 eppendymomas. The majorit y of gliomas (38/50) analyzed here retained both 17 p alleles. The frequenc y of p53 mutations was 13% in this group of tumors and increased to 50% (6/ 12) in tumors with one 17 p allele (P < 0.025). LOH on chromosome 10 was fo und in 35% (6/17) of high-grade astrocytomas, in 10% (1/10) of medulloblast omas, but in 0% of low-grade gliomas. EGFR gene amplification was found in 9 high-grade gliomas, 60% (6/9) of which also presented LOH for chromosome 10. Conclusions These results indicate that p53 inactivation is a common geneti c event in astrocytoma progression that may be more strongly associated wit h the progression of astrocytomas than with their origin. Absence of p53 mu tations in 50% of the tumors with one 17 p allele suggests that a tumor sup pressor gene other than p53 may be located on chromosome 17 p and involved in progression to malignancy of some gliomas. The loss of alleles on chromo some 10 and the amplification of the EGFR gene appear to be restricted to h igh-grade tumors, suggesting that these events may be related to tumor prog ression rather than initiation.