| Project/Area Number |
18590334
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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 |
Human pathology
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| Research Institution | Nagasaki University |
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Principal Investigator |
NAKASHIMA Masahiro Nagasaki University, Graduate School of Biomedical Sciences, Assistant Professor (50284683)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Atomic bomb survivors / Radiation / Thyroid cancer / 53BP1 / DNA damage response / Gene amplification / RET oncogene / FISH / ゲノム不安定性 / 癌 / 甲状腺 / 被爆者 |
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| Research Abstract |
RET/PTC rearrangement in papillary thyroid cancers (PTC) from A-bomb survivors : Although the expression of tubulin mRNA was evident in 89.5% of PTC by RT-PCR, neither RET/PTC1 nor PTC3 was detected in any cases.
FISH analysis for RET in PTC : We firstly demonstrated amplification of RET oncogene in a case of anaplastic thyroid cancer from A-bomb survivors who received internal irradiation therapy with 131I for previous thyroid cancer. RET amplification was also observed in radiation-induced papillary thyroid cancers and poorly differentiated thyroid cancers, suggesting the involvement of genomic instability during thyroid carcinogenesis.
Genomic instability in thyroid follicular epithelium from A-bomb survivors: The level of 53BP1 focus formation was significantly higher in cancers than normal follicular cells. These 53BP1 foci co-localized with upper stream pATM and downstream p53 molecules in cancer cells. A low level of 53BP1 foci formation could be detected also in follicular epithelium surrounding tumor, suggesting an initial stage during thyroid carcinogenesis.
BRAF mutation in PTC from A-bomb survivors : A hot spot point mutation BRAF T1799A was detected in 14.9% of PTC, while others were wild type. No significant association was revealed between A-bomb radiation and BRAF mutation.
RET amplification in PTC and genomic instability : RET amplification in PTC was only found in radiation-induced and high grade cases. During thyroid carcinogenesis, 53BP1 foci formation could be observed in follicular adenoma, and its expression altered into abnormal type with anaplastic transformation. Thus, genomic instability might be induced at the early stage and accelerated with progression of tumorigenesis. The type of 53BP1 expression in radiation-induced PTC was abnormal type, suggesting involvement of increased genomic instability in RET amplification.
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