2018 Fiscal Year Annual Research Report
Mitochondrial DNA deletions as a bioindicator of radiation exposure in papillary thyroid carcinoma
| Project/Area Number |
16K09805
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| Research Institution | Nagasaki University |
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Principal Investigator |
ログノビッチ タチアナ 長崎大学, 原爆後障害医療研究所, 助教 (30423643)
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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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| Keywords | mtDNA / mtDNA deletions / RNA-seq NGS |
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| Outline of Annual Research Achievements |
The aim of our study was 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 NGS as a potential individual molecular marker of radiation exposure.
Using primary cultures of human thyrocytes exposed to IR (from 0.5 to 5 Gy), we found a significant dose-dependent increase of mtDNA deletions, while mtDNA content and common deletion (CD) content did not change. Hence, IR can generate large-scale mtDNA deletions in thyrocytes after exposure.
To determine whether deletion-harboring fusion mtDNA species are expressed, and to compare the spectrum of mtDNA deletions with that in primary thyrocytes, we performed RNA-seq. For RNA-seq we used tumor and normal counterparts of radiation-induced and sporadic papillary thyroid carcinomas from exposed or non-exposed childhood patients, respectively.
In Tumor PTC samples we found more than 400 expressed mtDNA fusions sized from 1.9 to 15.1 kb, but only less than 20 of these fusions had high probability of expression as judged by the number of reads. The most frequent breakpoints in highly expressed mtDNA fusions were localized in CYTB, ND6, ND5, ND4, COX3, ATP6 and COX2 mtDNA genes. In Normal thyroid tissue counterparts we did not find such deletions.
The results of our study demonstrate that radiation-induced mtDNA deletions may persist for a long time after exposure, but only those whose size exceeds 1.9 kb are expressed.
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Research Products
(10 results)
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[Journal Article] Comparative Histopathologic Analysis of "Radiogenic" and "Sporadic" Papillary Thyroid Carcinoma: Patients Born Before and After the Chernobyl Accident.2018
Author(s)
Bogdanova TI, Saenko VA, Brenner AV, Zurnadzhy LY, Rogounovitch TI, Likhtarov IA, Masiuk SV, Kovgan LM, Shpak VM, Thomas GA, Chanock SJ, Mabuchi K, Tronko MD, Yamashita S.
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Journal Title
Thyroid
Volume: 28
Pages: 880-890
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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