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Mitochondrial DNA deletions as a bioindicator of radiation exposure in papillary thyroid carcinoma

Research Project

Project/Area Number 16K09805
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Endocrinology
Research InstitutionNagasaki University

Principal Investigator

ROGOUNOVITCH Tatiana  長崎大学, 原爆後障害医療研究所, 助教 (30423643)

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)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
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)
KeywordsmtDNA / Large-scale deletion / RNA-seq / mtDNA deletions / RNA-seq NGS / MiSeq NGS
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.

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。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (27 results)

All 2019 2018 2017 2016 Other

All Journal Article (10 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 9 results,  Open Access: 9 results) Presentation (16 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] Histopathological analysis of papillary thyroid carcinoma detected during ultrasound screening examinations in Fukushima2019

    • Author(s)
      Suzuki Shinichi、Bogdanova Tetiana I.、Saenko Vladimir A.、Hashimoto Yuko、Ito Masahiro、Iwadate Manabu、Rogounovitch Tatiana I.、Tronko Mykola D.、Yamashita Shunichi
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 2 Pages: 817-827

    • DOI

      10.1111/cas.13912

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Encapsulated Papillary Thyroid Tumor with Delicate Nuclear Changes and a KRAS Mutation as a Possible Novel Subtype of Borderline Tumor.2019

    • Author(s)
      Ohba K, Mitsutake N, Matsuse M, Rogounovitch T, Nishino N, Oki Y, Goto Y, Kakudo K.
    • Journal Title

      J Pathol Transl Med.

      Volume: 53 Issue: 2 Pages: 136-141

    • DOI

      10.4132/jptm.2018.12.07

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genetic Polymorphism Predisposing to Differentiated Thyroid Cancer: A Review of Major Findings of the Genome-Wide Association Studies2018

    • Author(s)
      Saenko Vladimir A.、Rogounovitch Tatiana I.
    • Journal Title

      Endocrinology and Metabolism

      Volume: 33 Issue: 2 Pages: 164-164

    • DOI

      10.3803/enm.2018.33.2.164

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparative Histopathologic Analysis of “Radiogenic” and “Sporadic” Papillary Thyroid Carcinoma: Patients Born Before and After the Chernobyl Accident2018

    • Author(s)
      Bogdanova Tetiana I.、Saenko Vladimir A.、Brenner Alina V.、Zurnadzhy Liudmyla Yu.、Rogounovitch Tatiana I.、Likhtarov Ilya A.、Masiuk Sergii V.、Kovgan Leonila M.、Shpak Victor M.、Thomas Geraldine A.、Chanock Stephen J.、Mabuchi Kiyohiko、Tronko Mykola D.、Yamashita Shunichi
    • Journal Title

      Thyroid

      Volume: 28 Issue: 7 Pages: 880-890

    • DOI

      10.1089/thy.2017.0594

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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.
    • Journal Title

      Thyroid

      Volume: 印刷中 Issue: 6 Pages: 811-818

    • DOI

      10.1089/thy.2016.0673

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Single-nucleotide polymorphisms predisposing to thyroid cancer: major findings of genome-wide association studies.2017

    • Author(s)
      Rogounovitch Tatiana, Saenko Vladimir
    • Journal Title

      Thyroid Cancer Explore

      Volume: 3(1) Pages: 25-31

    • Related Report
      2017 Research-status Report
  • [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.
    • Journal Title

      Endocrine Journal

      Volume: 64 Issue: 10 Pages: 977-993

    • DOI

      10.1507/endocrj.EJ17-0134

    • NAID

      130006186081

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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.
    • Journal Title

      Thyroid

      Volume: 27 Issue: 2 Pages: 224-235

    • DOI

      10.1089/thy.2015.0541

    • NAID

      120006987557

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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.
    • Journal Title

      Endocrine Journal

      Volume: 63 Issue: 5 Pages: 457-467

    • DOI

      10.1507/endocrj.EJ15-0629

    • NAID

      130005154197

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
    • Journal Title

      Endocrinology

      Volume: 印刷中 Issue: 5 Pages: 2182-2195

    • DOI

      10.1210/en.2015-2066

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Clinicopathological associations of BRAFV600E mutation in papillary thyroid carcinoma diagnosed in young adult patients exposed to Chernobyl radiation at a very young age2018

    • Author(s)
      Rogounovitch TI, Saenko VA, Frydman MV, Manskovskaya SV, Yamashita S
    • Organizer
      第91回 日本内分泌学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Comparative analysis of clinical and morphological characteristics according to BRAF mutational status in post-Chernobyl adult PTCs from Belarus2018

    • Author(s)
      Saenko V, Rogounovitch T, Frydman M, Mankovskaya S, Yamashita S
    • Organizer
      第61回 日本放射線影響学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The DIRC3 SNP does not associate with the risk for radiation-related thyroid cancer in children in contrast to other age or exposure-status groups from Belarus2018

    • Author(s)
      Rogounovitch TI, Saenko VA, Leonava TA, Drozd VM, Takahashi M, Kawaguchi T, Mitsutake N, Matsuda F, Yamashita S
    • Organizer
      第61回 日本放射線影響学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Association of BRAF mutational status with the chance of recurrence of papillary thyroid carcinoma in patients from Russia2018

    • Author(s)
      Saenko V, Rogounovitch T, Abrosimov A, Sidorin A, Rumyantsev P, Yamashita S
    • Organizer
      第61回日本甲状腺学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Clinical and morphological characteristics according to BRAF mutational status in post-Chernobyl young adult PTCs2018

    • Author(s)
      Rogounovitch T, Frydman M, Mankovskaya S,Yamashita S, Saenko V
    • Organizer
      第61回日本甲状腺学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Papillary Thyroid Carcinoma Associated with Post-Chernobyl Exposure to Radiation: a Comparative Analysis of Clinical and Morphological Characteristics According to BRAF Mutational Status in Young Adults of Belarus2018

    • Author(s)
      Mikhail Frydman, Tatiana Rogounovitch, Sviatlana Mankovskaya, Shunichi Yamashita, Vladimir Saenko
    • Organizer
      The 2nd International Symposium of the Network-type Joint Usage/Research Center for Radiation Disaster Medical Science
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Immunohistochemical Analysis of BRAF Mutational Status in the Papillary Thyroid Carcinoma with Special Reference to Recurrent Tumors2018

    • Author(s)
      Alexander Abrosimov, Tatiana Rogounovitch, Alexei Sidorin, Pavel Rumyantsev, Pavel Isaev, Kseniya Nizhegorodova, Anna Shinkarkina, Shunichi Yamashita, Vladimir Saenko
    • Organizer
      The 2nd International Symposium of the Network-type Joint Usage/Research Center for Radiation Disaster Medical Science
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] NOVEL RET/PTC REARRANGEMENT IDENTIFIED BY RNA-NGS IN A SPORADIC PEDIATRIC PTC2017

    • Author(s)
      Tatiana Rogounovitch, Vladimir Saenko, Svetlana Mankovskaya, Mikhail Frydman, Yuri Demidchik, Shunichi Yamashita
    • Organizer
      The 12th Asia and Oceania Thyroid Association Congress
    • Place of Presentation
      Busan Lotte Hotel, Busan, Korea
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Is the common SNP rs966423 at chromosome 2q35 etiology-specific and confers risk for sporadic thyroid cancer only?2017

    • Author(s)
      Rogounovitch TI, Saenko VA, Leonava TA, Drozd VM, Demidchik YE, Takahashi M, Kawaguchi T, Mitsutake N, Matsuda F, Yamashita S
    • Organizer
      第90回 日本内分泌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 福島の小児および思春期の甲状腺乳頭癌における新規融合癌遺伝子の同定2017

    • Author(s)
      井山慶大、光武範吏、松瀬美智子、タチアナ ログノビッチ、ウラジミール サエンコ、鈴木啓司、芦澤舞、大河内千代、鈴木聡、水沼廣、福島俊彦、鈴木眞一、山下俊一
    • Organizer
      第90回 日本内分泌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Is the common SNP rs966423 at chromosome 2q35 etiology-specific and confers risk for sporadic thyroid cancer only?2017

    • Author(s)
      Rogounovitch TI, Saenko VA, Leonava TA, Drozd VM, Takahashi M, Kawaguchi T, Mitsutake N, Matsuda F, Yamashita S
    • Organizer
      第60回日本甲状腺学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Histopathological features of sporadic papillary thyroid carcinoma in children and adolescents of Japan and Ukraine: a comparative analysis2017

    • Author(s)
      Bogdanova T, Saenko V, Hirokawa M, Ito M, Zurnadzhy L, Rogounovitch T, Miyauchi A, Tronko M, Yamashita S
    • Organizer
      第60回日本甲状腺学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Studies of molecular features of radiation-induced and sporadic papillary thyroid carcinomas2016

    • Author(s)
      タチアナログノビッチ
    • Organizer
      第59回日本甲状腺学会学術集会
    • Place of Presentation
      虎ノ門ヒルズフォーラム (東京都・港区)
    • Year and Date
      2016-11-03
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] SNP association with risk for sporadic papillary thyroid carcinoma in Kazakh population2016

    • Author(s)
      Zhanna Mussazhanova 、Tatiana Rogounovitch 、Vladimir Saenko 、Ainur Krykpayeva 、Bayurzhan Azizov 、Mukhtar Tuleutayev 、 Maira Espenbetova 、山下 俊一 、中島 正洋
    • Organizer
      第59回日本甲状腺学会学術集会
    • Place of Presentation
      虎ノ門ヒルズフォーラム (東京都・港区)
    • Year and Date
      2016-11-03
    • Related Report
      2016 Research-status Report
  • [Presentation] Novel RET/PTC rearrangement identified by RNA-NGS in a sporadic pediatric PTC2016

    • Author(s)
      ログノビッチ タチアな1, サエンコウラジミル, マンコブスカヤ スベトラナ, フリドマン ミハイル4, デミドチック ユリ, 山下俊一
    • Organizer
      第89回日本内分泌学会学術総会
    • Place of Presentation
      国立京都国際会館 (京都府・京都市)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Research-status Report
  • [Presentation] 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 carcinoma2016

    • Author(s)
      ニキツキ アレクサンドル、サエンコ ウラジイミル、ログノビチ タチアナ、ビチコブ アンドレイ、高橋めい子、吉浦孝一郎、光武範吏、川口喬久、松瀬美智子、ドロズド ワレンチナ、デミドチック ユリ、 西原永潤、廣川満良、宮内昭、ルバのビッチ アレクサンドル、松田文彦、山下俊一
    • Organizer
      第89回日本内分泌学会学術総会
    • Place of Presentation
      国立京都国際会館 (京都府・京都市)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Research-status Report
  • [Remarks] 長崎大学原研医療

    • URL

      http://www-sdc.med.nagasaki-u.ac.jp/drms/

    • Related Report
      2018 Annual Research Report 2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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