| Budget Amount *help |
¥15,500,000 (Direct Cost: ¥15,500,000)
Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥12,000,000 (Direct Cost: ¥12,000,000)
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| Research Abstract |
Dpite great efforts in basic life science and clinical esearch, little progress has been made in mproving the prognosis for patients with glioblastomas. urgical cure of gliomas is impossible in practice because of their high infiltrating activity. The clinical course is dependent upon the biological behavior of the tumor cells. There is increasing evidence that the accumulation of genetic and epigenetic alterations is essential for tumor initiation and progression. Conventional comparative genomic hybridization(metaphase-CGH)_4 has been widely used to screen for chromosomal gains and losses throughout the entiregenome of a tumor. Microarraybased CGH (array-CGH) is a recently developed genomicanalysis technology that enables high-throughputscreening of gene aberrations with sensitivity to detect single gene copy changes. In this study, we employed array CGH formapping of copy number alterations in glioblastomas and analyzed the potential correlation between genomic changes and prognosis
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of patients. We examined whole genomic aberrations of biopsied samples from glioblastomas by array-based comparative genomic hybridization analysis. The highest frequencies of copy number gains were observed on RFC2 (73.3%), EGFR (63.2%), and FGR, ELN, CDKN1C, FES, TOP2A, and ARSA (57.9% each). The highest frequencies of copy number losses were detected on TBR1(52.6%), BMI1 (52.6%), EGR2 (47.4%), DMBT1 (47.4%), MTAP (42.1%), and FGFR2 (42.1%). The copy numbergains of CDKN1C and INS and the copy number losses of TBR1 were significantly correlated with longer survival of patients. High-level amplifications were identified on EGFR, SAS/CDK4, PDGFRA, MDM2, and ARSA. These genes are assumed to be involved in tumorigenesis or progression of glioblastomas. The present study indicates that array-based comparative genomic hybridization analysis has great potential for assessment of copy number changes and altered chromosomal regions of brain tumors. Furthermore, we show that nonlinear analysis methods of whole genome copy number profiles may provide prognostic information about glioblastoma patients. Less
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