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 factor 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 grades using the polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) assay, and were confirmed by direct sequencing. LOH for chromosome 10, 17 p 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 eppendymoblastoma but in none of the 10 medulloblastomas and 7 eppendymomas. The majority of gliomas (38/50) analyzed here retained both 17 p alleles. The frequency 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 found in 35% (6/17) of high-grade astrocytomas, in 10% (1/10) of medulloblastomas, 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 genetic event in astrocytoma progression that may be more strongly associated with the progression of astrocytomas than with their origin. Absence of p53 mutations in 50% of the tumors with one 17 p allele suggests that a tumor suppressor 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 chromosome 10 and the amplification of the EGFR gene appear to be restricted to high-grade tumors, suggesting that these events may be related to tumor progression rather than initiation.
Jin
W
W
State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, Nanjing University, Nanjing 210093, China. xutnf@nju.edu.cn
Xu
X
X
Yang
T
T
Hua
Z
Z
D001932:Brain Neoplasms / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10; D002886:Chromosomes, Human, Pair 17; D005784:Gene Amplification; D018773:Genes, erbB-1; D016158:Genes, p53; D005910:Glioma / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation