STUDY ON THE DIAGNOSIS AND THERAPY OF BRAIN TUMORS IN TERMS OF GENETIC ENGINEERING

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In the present study, we have investigated the altered expression and gene mutation of a tumor suppressor gene, p53, in order to clarify whether p53 gene mutation is actually involved in tumorigenesis and development of human glial tumors. As the first step, 7 different human glioma cell lines were examined by immunocytochemistry and PCR-SSCP analysis. All of the 7 cell llines examined showed abnormal expression of p53 protein and this altered gene expression was ascribed to the point mutations occurred in p53 gene of glioma cells. As the second step, 50 brain tumor specimens obtained at craniotomy were examined by PCR-SSCP analysis. Three cases (38%) out of 8 astrocytomas and 5 (31%) out of 16 glioblastomas revealed point mutations or deletions of p53 gene, respectively, though the sites of the mutations or deletions were different in indivedual cases. This results indicate that the mutation rate of p53 gene is similar between low grade and high grade gliomas, and that p53 gene mutations are directly invovled in the tumorigenesis of al lest one third of human glial tumors. Thus, p53 seems to be very useful in the DNA diagnosis of human brain tumors, especially glial tumors. On the other hand, it is essential to obtain the CNS specific expression vector sytem in terms of GFAP promoter in establishing the gene therapy for malignant gliomas. In the present study, the detailed sequence of enhancer in the GFAP promoter region has been determined and furthermore, the tandem constructs consisting of 2 or 4 enhancers of GFAP revealed 4 to 5 times increase in transcription rate, indicating its potential use in CNS gene therapy in the fulure.