Mitochondrial DNA deletions as a bioindicator of radiation exposure in papillary thyroid carcinoma
| Project/Area Number |
16K09805
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Nagasaki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中沢 由華 名古屋大学, 環境医学研究所, 助教 (00533902)
サエンコ ウラジミール 長崎大学, 原爆後障害医療研究所, 准教授 (30343346)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | mtDNA / Large-scale deletion / RNA-seq / mtDNA deletions / RNA-seq NGS / MiSeq NGS |
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| Outline of Final Research Achievements |
The aim of our study is to evaluate the mitochondrial DNA (mtDNA) deletion profile in radiation-induced and sporadic PTCs and in exposed to ionizing radiation (IR) human primary thyrocytes using next-generation sequencing as a potential individual molecular marker of radiation exposure. Using primary cultures of human thyrocytes exposed to IR (from 0.5 to 10 Gy), we found a significant dose-dependent increase of mtDNA deletions, while mtDNA content and common deletion (CD) content did not change. In radiation-induced PTC the number of large-scale deletions is higher than in sporadic.
In radiation-induced PTCs deleted mtDNA may persist for a long time after exposure, but only those whose size exceeds 1.9 kb are highly expressed. These findings suggest that RNA transcripts with large deletions involving CYTB, ND6, ND5, ND4, COX3, ATP6 and COX2 mtDNA genes may be a potential marker of radiation etiology of papillary thyroid carcinoma in exposed patients.
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| Academic Significance and Societal Importance of the Research Achievements |
CYTB、ND6、ND5、ND4、COIII、ATP6及びCOⅡのmtDNA遺伝子領域における『大きな欠失（large-scale deletions）』を有するRNA転写産物が、放射線誘発PTC特異的な分子マーカーとなる可能性が示唆された。
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] Identification of Three Novel Fusion Oncogenes, SQSTM1/NTRK3, AFAP1L2/RET, and PPFIBP2/RET, in Thyroid Cancers of Young Patients in Fukushima.2017
Author(s)
Iyama K, Matsuse M, Mitsutake N, Rogounovitch T, Saenko V, Suzuki K, Ashizawa M, Ookouchi C, Suzuki S, Mizunuma H, Fukushima T, Suzuki S, Yamashita S.
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Journal Title
Thyroid
Volume: 印刷中
Issue: 6
Pages: 811-818
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Comparative histopathological analysis of sporadic pediatric papillary thyroid carcinoma from Japan and Ukraine2017
Author(s)
Bogdanova TI, Saenko VA, Hirokawa M, Ito M, Zurnadzhy LY, Hayashi T, Rogounovitch TI, Miyauchi A, Tronko MD, Yamashita S.
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Journal Title
Endocrine Journal
Volume: 64
Issue: 10
Pages: 977-993
DOI
NAID
ISSN
0918-8959, 1348-4540
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Genotype Analyses in the Japanese and Belarusian Populations Reveal Independent Effects of rs965513 and rs1867277 but Do Not Support the Role of FOXE1 Polyalanine Tract Length in Conferring Risk for Papillary Thyroid Carcinoma.2017
Author(s)
Nikitski AV, Rogounovitch TI, Bychkov A, Takahashi M, Yoshiura KI, Mitsutake N, Kawaguchi T, Matsuse M, Drozd VM, Demidchik Y, Nishihara E, Hirokawa M, Miyauchi A, Rubanovich AV, Matsuda F, Yamashita S, Saenko VA.
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Journal Title
Thyroid
Volume: 27
Issue: 2
Pages: 224-235
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Association between p53-binding protein 1 expression and genomic instability in oncocytic follicular adenoma of the thyroid2016
Author(s)
Mussazhanova Z, Akazawa Y, Matsuda K, Shichijo K, Miura S, Otsubo R, Oikawa M, Yoshiura K, Mitsutake N, Rogounovitch T, Saenko V, Kozykenova Z, Zhetpisbaev B, Shabdarbaeva D, Sayakenov N, Amntayev B, Kondo H, Ito M, Nakashima M.
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Journal Title
Endocrine Journal
Volume: 63
Issue: 5
Pages: 457-467
DOI
NAID
ISSN
0918-8959, 1348-4540
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Targeted Foxe1 overexpression in mouse thyroid causes the development of multinodular goiter but does not promote carcinogenesis.2016
Author(s)
Nikitski A, Saenko V, Shimamura M, Nakashima M, Matsuse M, Suzuki K, Rogounovitch T, Bogdanova T, Shibusawa N, Yamada M, Nagayama Y, Yamashita S, Mitsutake N
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Journal Title
Endocrinology
Volume: 印刷中
Issue: 5
Pages: 2182-2195
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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