KOCHI Masato KUMAMOTO MEDICAL DEPARTMENT, KUMAMOTO UNIVERSITY, ASSOCIATE PROFESSOR, 医学部, 助教授 (70178218)
SAYA Hideyuki KUMAMOTO MEDICAL DEPARTMENT, KUMAMOTO UNIVERSITY, PROFESSOR, 医学部, 教授 (80264282)
西 徹 熊本大学, 医学部・附属病院, 助手 (00264309)
竹島 秀雄 熊本大学, 医学部, 助手 (70244134)
|Budget Amount *help
¥39,220,000 (Direct Cost: ¥37,300,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2001: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2000: ¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1999: ¥23,500,000 (Direct Cost: ¥23,500,000)
To establish rational therapy for malignant gliomas (MG) based on their genetic background, we performed molecular genetic analysis to determine factors related to the initiation and progression of these tumors. We studied p53 mutation(s), p16 homozygous deletions) (HD), the amplification of epidermal growth factor receptor (EGFR), and, loss of heterozygosity, (LOH) for chromosome 10.
Our samples consisted of 15 pilocytic astrocytomas (PA), 20 diffuse astrocytomas (A), 55 anaplastic astrocytomas (AA), and 135 glioblastomas multiforme (GBM).
In PA, there were no genetic abnormalities except in special cases associated with neurofibromatosis-1. Mutation of p53 was observed in 29 % of A, 50 % of AA, and 35 % of GBM. HD of p16 was observed in 10 % of AA and 31 % of GBM; 9 % of AA and 31 % of GBM manifested EGFR amplification; 36 % of AA and 63 % of GBM had LOH for chromosome 10. We found that LOH for chromosome 10, especially the PTEN locus, was an unfavorable prognostic factor in patient with GBM (Tada K, et al: J. Neurosurg. 95, 2001), and that HD of p16 was also an unfavorable prognostic factor in male GBM patients (Kamiryo T, et al: J. Neurosurg. (in press), 2002).
Based on analysis of the 4 genetic alterations, we classified MG into 7 subtypes. The combination of EGFR amplification and LOH for chromosome 10 was the most unfavorable prognostic indicator in patient with GBM. We conclude that it is necessary to develop novel therapies, for example gene therapy, to treat such patients with MG.