| Project/Area Number |
14380256
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | Nagasaki University |
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Principal Investigator |
SAENKO Vladimir Nagasaki University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (30343346)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Shunichi Nagasaki University, Graduate School of Biomedical Sciences, professor, 大学院・医歯薬学総合研究科, 教授 (30200679)
NAMBA Hiroyuki Nagasaki University, Graduate School of Biomedical Sciences, Associate professor, 大学院・医歯薬学総合研究科, 助教授 (80237635)
OHTSURU Akira Nagasaki University, Hospital of Medicine and Dentistry, Associate professor, 医学部・歯学部附属病院, 助教授 (00233198)
TAKAMURA Noboru Nagasaki University, Graduate School of Biomedical Sciences, Associate professor, 大学院・医歯薬学総合研究科, 助教授 (30295068)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2004: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥5,100,000 (Direct Cost: ¥5,100,000)
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| Keywords | Thyroid Tumor / Mitochondrial DNA / Radiation / Papillary Thyroid Cancer / Mutation / Large-scale Deletions / Genotype-Phenotype correlation / 甲状腺がん / ミトコンドリア / BRAF / 分子診断 / 分子標的治療 / 発がん機構 |
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| Research Abstract |
Molecular events underlying radiation-induced thyroid cancer are poorly understood. Therefore, elucidation of the molecular radiation signatures is one of the urgent tasks to understand pathogenesis of thyroid cancer in exposed individuals. In our investigation within the project, we evaluated general and mutational status of mitochondrial DNA(mtDNA) in the series of post-Chernobyl and control thyroid papillary cancer(PTC) to determine whether specific alterations in mtDNA can be linked to possible radiation fallout in the affected population. We focused on relative mtDNA content, prevalence and level of common deletion(CD) and large scale deletions in mtDNA.
Our data demonstrate that elevated relative mtDNA content can be found in tumor tissue in most of cases of PTCs without correlation with the level of radioiodine contamination of patients' residency or with clinicopathological characteristics. Elevated level of CD was predominantly found in tumor tissue of the radiation associated group but not in sporadic PTCs, however no correlation was noted with clinicopathological parameters, radioiodine contamination and relative mtDNA content. The quantity of large scale deletions in mtDNA was elevated in most rumor tissues especially in the radiation associated group and tended to correlate with the level of radiopollutant in PTC. Most importantly, a highly significant positive correlation between the presence of large scale mtDNA deletions and relative mtDNA content was found in radiation-associated tumors.
We concluded that concordant increase of both relative mtDNA level and number of mtDNA deletions may be specific to radiation associated PTC and comprise a distinctive molecular feature of radiation-associated thyroid cancer.
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