2005 Fiscal Year Final Research Report Summary
Identification of novel biological markers for the tailor-made treatment of oligodendrogial tumors
| Project/Area Number |
16591465
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Chiba Cancer Research Institute |
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Principal Investigator |
IUCHI Toshihiko Chiba Cancer Center Research Institution, Div. of Biochemistry, 生化学研究部・業務研究員 (80370881)
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| Project Period (FY) |
2004 – 2005
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| Keywords | oligodendroglial tumor / molecular marker / loss of heterozygosity / cDNA chip / molecular diagnosis / surivival |
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| Research Abstract |
For narrowing down the candidate gene locus on the short arm of the chromosome 1 (1p) which correlate with the progression of oligodendroglial tumors, we analyzed the status of 1p in 64 oligodendroglial and 87 astrocytic tumors using micro-satellite marker method. The frequency of loss of heterozygosity (LOH) of 1p was extremely higher (92.8%) in the oligodendroglial tumors than astrocytic tumors (26.4%). Furthermore, the majority of the oligodendroglial cases showed long terminal deletion of 1p (72.5), in contrast with the low incidence of long deletion in astrocytic tumors (6.9%). We defined 3 common deleted regions in 1p, 1p34-35, 1p36.11-36.12 and 1p36.22-36.32 in oligodendroglial tumors. We found that these regions were also deleted in astorcytic tumors, but its' incidence was low. Among these 3 regions, 1p34-35 was most frequently deleted in oligodendroglial tumos. In this region, 2 known and 2 un-known genes were localized. We evaluated the expression of these 4 genes by RT-PCR
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and found that the expression level of these genes was not different between oligodendroglial and astorcytic tumors. On the other hand, LOH of 1p36.11-36.12 was correlated with the survival of patients with both the oligodendroglial and astrocytic tumors. These data suggested that the existence of gene(s) which correlated with the aggressiveness of tumors localized in this region.
Next, we evaluated the different expression levels of genes using cDNA chip. The expression profile of genes was clearly different between oligodendroglial and astrocytic tumors. Among the 563 genes, 240 genes showed significant difference in the expression level between these tumors. Among these 240 genes, we picked up 5 genes which met all of the following conditions, 1) the expression level of the gene was significantly higher in oligodendroglial than astrocytic tumors, 2) the expression level of the gene in the astrocytic tumors was same or lower than the level in normal brain tissue, 3) the significance of the difference in expression levels between oligodendroglian and astrocytic tumors was extremely high (p<0.0001). We re-classificated the cases owing to the expression levels of these 5 genes. With this molecular maker classification, 5 cases of oligodendroglial tumor were diagnosed as astrocytic tumor, and 2 cases of astrocytic tumor were diagnosed as oligodendroglial tumor. The frequency of 1p LOH in these 5 tumors whose diagnosis was changed from oligodendroglial to astocytic tumor was significantly lower (40%) than the remaining oligodendroglial tumors diagnosed as oligodendroglial also by molecular marker classification(100%, p=0.015). The survival of patient with oligodendroglial tumors was significantly better than that with astocytic tumors, but the significance of the difference was much more significant by molecular marker method than classical morphological classification. The relative risk of patients with astrocytic tumors was 4.11 by morphological diagnosis but 8.11 by morcular marker method. These data suggested that the molecular marker classification demonstrated here more precisely reflects the biological character of the tumors and was more useful in the clinical diagnosis. Less
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