| Project/Area Number |
16591786
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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 |
Pediatric surgery
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
YAMAOKA Hiroaki Hiroshima University, Hospital, Assistant Professor, 病院, 講師 (90311810)
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| Co-Investigator(Kenkyū-buntansha) |
HIYAMA Eiso Hiroshima Univ., Natural Science Center for Basic Research and Development, Professor, 教授 (00218744)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | neuroblastoma / caspase 8 / methylation / microarray / unfavorable / promoter |
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| Research Abstract |
Neuroblastoma can be subdivided into favorable and unfavorable subtypes and the optimal therapeutic strategy is selected also on the basis of the genetic characteristics of each tumor. Caspase 8 signals through the formation of a death-inducing signaling complex when Fas is activated by Fas ligand on the cell surface. Recently, the gene of caspase 8 (CASP8) is frequently inactivated in neuroblastoma. The gene is silenced through DNA metylation as well as genetic deletion. Aberrant methylation of CpG island-stretches within a promoter, causing silencing of tumor suppressor genes, is a widespread phenomenon in cancer cell. Methylation density in promoter CpG island was indicated to be important for gene silencing rather than methylation that occurred at a limited number of CpG island in the promoter.
Several groups have recently shown that the methylation status can be precisely achieved by microarray-based technologies. In this study, we produced a poly carbodiimide-coated slide (Carbo Station^<TM>, Nisshinbo Industries Inc.) platform consists of a glass slide that has been produced by coating microscope slides with poly carbodiimide to detect methlation of 5' flanking region of CASP8.
We made the microarray which was enable to judge the presence of the metylation at six places of CASP 8 5' flanking region without any special machine. Neuroblastoma tumor tissues used in this study were surgically removed at Hiroshima University and affiliate hospitals. Tumor tissue DNA samples was performed by bisulfite modification and amplified by PCR-method and analized by the microarray. We analyzed the methylation status of tumor tissue DNA and corresponding peripheral blood lymphocyte from 50 patients.
In this study, significant difference was examined between favorable and unfavorable subtypes. This custom microarray might be useful fro bedside judgement of neuroblastoma biology
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