Identification of genomic radiation signature using long-read sequencing
| Project/Area Number |
20K21718
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 58:Society medicine, nursing, and related fields
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| Research Institution | Nagasaki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 啓司 長崎大学, 原爆後障害医療研究所, 准教授 (00196809)
荻 朋男 名古屋大学, 環境医学研究所, 教授 (80508317)
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| Project Period (FY) |
2020-07-30 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 放射線 / ゲノム / HPRT変異クローン / HPRTクローン |
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| Outline of Research at the Start |
放射線被ばくによって癌が発生するのは明らかであるが、あるひとつの癌が放射線で引き起こされたものか、その他の原因で起きたものかを区別する方法は今のところない。放射線はクラスター損傷と呼ばれる複雑な異常をDNAに引き起こし、マイクロホモロジーを伴う欠失や逆位を生じさせるとされるが、これらを全ゲノムレベルで解析する手法は今までなかった。本研究では、様々な線量の放射線を照射し樹立したHPRT変異細胞クローンと、新規技術であるロングリードシークエンシングを用い、上記の欠失や逆位を全ゲノムレベルで解析し、放射線刻印とも呼べる放射線特異的なゲノム変化の有無を明らかにする。
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| Outline of Final Research Achievements |
Two different platforms of next generation sequencing, short- and long-read sequencing, revealed the following characteristics of radiation-induced genomic variants in human normal cells: 1) Deletions of various sizes increased in a dose-dependent manner. 2) At high doses, very long deletions (hundreds of thousands to megabases or more) occurred. 3) Many of the deletions had no homology sequence at break points. Deletions by high doses often contained a distinct sequence at the junction. 4) Single nucleotide substitutions also increased but were not dose dependent. 5) Single nucleotide substitutions contained mutational signatures suggestive of oxidative damage. However, we were unable to identify mutations that were completely specific to radiation exposure.
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| Academic Significance and Societal Importance of the Research Achievements |
DNA配列決定法の技術的な進歩により、DNAの配列変化をゲノムワイドに調べることが可能となってきた。放射線被ばくは、発がんリスクを上昇させることは疫学的に明らかであり、放射線によるゲノム変異がその誘因であると考えられている。本研究において、ヒト正常培養細胞で、放射線によって生じるゲノム変異の特徴の多くが詳細に明らかになった。これらの異常が、発癌の第一歩となる可能性が高い。本研究成果は、放射線による生物学的影響、遺伝子異常、発癌などの他の研究にも活かせる基盤的データとなると思われる。
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Report
(4 results)
Research Products
(30 results)
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[Journal Article] Clinicopathological Implications of the BRAFV600E Mutation in Papillary Thyroid Carcinoma of Ukrainian Patients Exposed to the Chernobyl Radiation in Childhood: A Study for 30 Years After the Accident2022
Author(s)
Zurnadzhy L, Bogdanova T, Rogounovitch TI, Ito M, Tronko M, Yamashita S, Mitsutake N, Chernyshov S, Masiuk S, Saenko VA.
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Journal Title
Front. Med., 26 April 2022
Volume: -
Pages: 882727-882727
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Comprehensive analysis for detecting radiation-specific molecules expressed during radiation-induced rat thyroid carcinogenesis.2021
Author(s)
Kurohama H, Matsuda K, Kishino M, Yoshino M, Yamaguchi Y, Matsuu-Matsuyama M, Kondo H, Mitsutake N, Kinoshita A, Yoshiura KI, Nakashima M.
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Journal Title
J Radiat Res.
Volume: 62
Issue: Supplement_1
Pages: i78-i87
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Preoperative detection of the TERT promoter mutations in papillary thyroid carcinomas2021
Author(s)
Nakao T, Matsuse M, Saenko V, Rogounovitch T, Tanaka A, Suzuki K, Higuchi M, Sasai H, Sano T, Hirokawa M, Miyauchi A, Kawakami A, Mitsutake N.
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Journal Title
Clinical Endocrinology
Volume: 95
Issue: 5
Pages: 790-799
DOI
Related Report
Peer Reviewed
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[Journal Article] Position paper from the Japan Thyroid Association task force on the management of low-risk papillary thyroid microcarcinoma (T1aN0M0) in adults2021
Author(s)
Kazuhiko Horiguchi, Yusaku Yoshida, Kenji Iwaku, Naoya Emoto, Toshihiko Kasahara, Junichiro Sato, Hiroki Shimura, Hisakazu Shindo, Satoru Suzuki, Hidekazu Nagano, Fumihiko Furuya, Noriko Makita, Fumihiko Matsumoto, Katsunori Manaka, Norisato Mitsutake, Megumi Miyakawa, Susumu Yokoya and Iwao Sugitani
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Journal Title
Endocrine Journal
Volume: 68
Issue: 7
Pages: 763-780
DOI
NAID
ISSN
0918-8959, 1348-4540
Related Report
Peer Reviewed / Open Access
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[Journal Article] Papillary thyroid carcinoma in Ukraine after Chernobyl and in Japan after Fukushima: different histopathological scenarios.2020
Author(s)
Bogdanova TI, Saenko VA, Hashimoto Y, Hirokawa M, Zurnadzhy LY, Hayashi T, Ito M, Iwadate M, Mitsutake N, Rogounovitch T, Sakamoto A, Naganuma H, Miyauchi A, Tronko MD, Thomas G, Yamashita S, Suzuki S:
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Journal Title
Thyroid
Volume: 308
Issue: 9
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The Clinicopathological Results of Thyroid Cancer With BRAFV600E Mutation in the Young Population of Fukushima.2020
Author(s)
Iwadate M, Mitsutake N, Matsuse M, Fukushima T, Suzuki S, Matsumoto Y, Ookouchi C, Mizunuma H, Nakamura I, Nakano K, Sakamoto A, Hirokawa M, Ito M, Naganuma H, Hashimoto Y, Shimura H, Yamashita S, Suzuki S
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Journal Title
J Clin Endocrinol Metab
Volume: 105
Issue: 12
Pages: 573-573
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome2020
Author(s)
Oka Y, Hamada M, Nakazawa Y, ..., Tanaka M, Suganami T, Nakada S, Mitsutake N, Hara Y, Kato K, ..., Kaneko H, Matsumoto N, Matsuda F, Matsuo K, Takahashi Y, Mashimo T, Kojima S, Ogi T
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Journal Title
Science Advances
Volume: 6
Issue: 51
Pages: 7197-7197
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] チェルノブイリと福島の甲状腺がんにおける様々な病理学的シナリオ2020
Author(s)
サエンコ ウラジミール, ボグダノワ タチアナ, 橋本 優子, 廣川 満良, リュドミラ ズルナドジ, 林 俊哲, 伊東 正博, 岩館 学, 光武 範吏, ログノビッチ タチアナ, 坂本 穆彦, 長沼 廣, 宮内 昭, トロンコ ミコラ, トマス ジュラルディン, 山下 俊一, 鈴木 眞一
Organizer
第63回 日本放射線影響学会 年次大会
Related Report
Invited
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