| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2005: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2004: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Research Abstract |
Over 60 gliomas were resected and analyzed. The diagnosis was performed in combination with genetic analysis on chromosomes 1p/19q/10q, which were known to correlate with oligodendroglial histological features and expression status of neuron-related genes in our previous studies. While treating the patients in the same protocol (PAV/RT 60Gy for GBM and PAV only for oligodendroglial tumors), clinical response was closely monitored. We attempted primary cultures for more than 10 gliomas. However, the established cultured cells showed different genetic alterations from the original tumors. Cells from 1p/19q-losing gliomas (n=3) did not show 1p/19q loss, which did not allow us to study gene-expression changes after chemotherapy in vitro, as was proposed in the project design. Meanwhile, the similar phenomenon, loss of "1p/19qloss" at the recurrence of oligodendroglioma, was detected in 2 cases. The underlying mechanisms for this interesting phenomenon should be examined in the future.
Whole
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-genome examination for allele-specific copy number changes using Gene Imbalance Mapping method (GIM) developed by Aburatani et al. was performed on 22 glioma samples. In oligodendrogliomas, GIM clearly showed that pure low grade oligodendrogliomas are the tumors harbor whole arm losses of 1p and 19q as their only genetic alterations. With histological changes to more anaplastic morphology, oligodendrogliomas show other genetic alterations such as 14q loss, 4p/4q loss, 9p loss, gradually becoming anaplastic oligodendrogliomas. Progression from grade 2 to 3 is therefore rather continuous, and GIM is an excellent method for the diagnosis of oligodendrogliomas. In glioblastomas, numerous loci showing homozygous deletion was detected, where currently unidentified tumor suppressor genes may be located. One such loci, 12q, was picked up and a few number of candidate genes are now being evaluated.
Unfortunately, the clinical data including survival are not yet obtained at this point, and comparison of genetic analysis and clinical response, the center theme of this project, should await summarization of clinical data. Less
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