Establishment of Chernobyl paraffin-embedded tissue Bank and discovering of new oncogene

• Project/Area Number: 24406031
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 海外学術
• Research Field: Endocrinology
• Research Institution: Nagasaki 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): NAKASHIMA Masahiro 長崎大学, 原爆後障害医療研究所, 教授 (50284683) ; SAENKO Vladimir 長崎大学, 原爆後障害医療研究所, 准教授 (30343346) ; SHIBATA Yoshisada 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (40010954)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2012: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
• Keywords: 小児甲状腺乳頭癌 / パラフィン組織バンク / 次世代シーケンシング / TBL1XR1/RET / 新規癌遺伝子

Outline of Final Research Achievements

During this study we collected from affected after Chernobyl fallout territories of Belarus and Ukraine paraffin-embedded tissues, frozen samples (if available) and blood samples from the most aggressive (young age of exposure and short-latent period) pediatric PTCs (operated from 1990 and until October 1998), which are not included in the Chernobyl Tissue Bank and established the Paraffin Tissue Bank. For all collected PTC samples we made data base of patients includes demographic, clinical and morphological information.
Using RNA-NGS technique we discovered a new RET rearrangement (TBL1XR1/RET) in pediatric PTC from Belarus. In vitro irradiation of human thyroid cells was able to induce TBL1XR1/RET rearrangement. The occurrence of TBL1XR1/RET rearrangement in PTC of sporadic and radiation-related etiology suggests that it may likely be induced by different genotoxic insults, one of which could be ionizing radiation.

Research Products

• [Journal Article] Bone mineral density in treated at a young age for differentiated thyroid cancer after Chernobyl female patients on TSH-suppressive therapy receiving or not Calcium-D3 supplementation (2015)
  • Author(s): Leonova TA, Drozd VM, Saenko VA, Mine M, Biko J, Rogounovitch TI, Takamura N, Reiners C, Yamashita S.
  • Journal Title: Endocrine Journal Volume: 62 Issue: 2 Pages: 173-182
  • DOI: 10.1507/endocrj.EJ14-0408
  • NAID: 130004713043
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The common genetic variant rs944289 on chromosome 14q13.3 associates with risk of both malignant and benign thyroid tumors in the Japanese population. (2015)
  • Author(s): Rogounovitch TI, Bychkov A, Takahashi M, Mitsutake N, Nakashima M, Nikitski AV, Hayashi T, Hirokawa M, Ishigaki K, Shigematsu K, Bogdanova T, Matsuse M, Nishihara E, Minami S, Yamanouchi K, Ito M, Kawaguchi T, Kondo H, Takamura N, Ito Y, Miyauchi A, Matsuda F, Yamashita S, Saenko VA.
  • Journal Title: Thyroid Volume: 25 Issue: 3 Pages: 333-340
  • DOI: 10.1089/thy.2014.0431
  • NAID: 120006987147
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Morphological difference in adult thyroid papillary carcinoma between Japan and Ukraine (2014)
  • Author(s): Ito M, Bogdanova T, Zurnadzhy L, Saenko V, Rogounovitch T, Mitsutake N, Kondo H, Maeda S, Nakashima M, Tronko M, Yamashita S.
  • Journal Title: Endocrine Journal Volume: 61 Issue: 12 Pages: 1221-1228
  • DOI: 10.1507/endocrj.EJ14-0239
  • NAID: 130004690931
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] Radiation-associated small cell neuroendocrine carcinoma of the thyroid: a case report with molecular analyses. (2014)
  • Author(s): Mussazhanova Z, Miura S, Stanojevic B, Rogounovitch T, Shiraishi T, Kurashige T, Shichijo K, Kaneko K, Takahashi H, Ito M, Nakashima M
  • Journal Title: Thyroid Volume: 24 Issue: 3 Pages: 593-598
  • DOI: 10.1089/thy.2013.0214
  • NAID: 120006986646
  • Peer Reviewed
• [Journal Article] Patterns of FOXE1 expression in papillary thyroid carcinoma by immunohistochemistry. (2013)
  • Author(s): Bychkov A
  • Journal Title: Thyroid Volume: 未定 Issue: 7 Pages: 817-828
  • DOI: 10.1089/thy.2012.0466
  • Peer Reviewed
• [Journal Article] Significance of p53-binding protein 1 (53BP1) expression in thyroid papillary microcarcinoma: association with BRAFV600E mutation status. (2013)
  • Author(s): Mussazhanova Z, Matsuda K, Naruke Y, Mitsutake N, Stanojevic B, Rogounovitch T, Saenko V, Suzuki K, Nishihara E, Hirokawa M, Ito M, Nakashima M.
  • Journal Title: HIstopathology Volume: 63 Issue: 5 Pages: 726-734
  • DOI: 10.1111/his.12233
  • Peer Reviewed
• [Journal Article] Patterns of FOXE1 expression in papillary thyroid carcinoma byImmunohistochemistry (2012)
  • Author(s): Bychkov A, et al.
  • Journal Title: 長崎医学会雑誌 Volume: 87 Pages: 273-276
• [Presentation] Novel RET/PTC rearrangement identified by RNA-NGS in a sporadic pediatric PTC from Belarus (2014)
  • Author(s): T.Rogounovitch, V.Saenko, S.Mankouskaya, M. Fridman, Yu.Demidchik, S.Yamashita
  • Organizer: 第57回 日本甲状腺学会学術集会
  • Place of Presentation: ナレッジキャピタル コングレコンベンションセンター（大阪府大阪市）
  • Year and Date: 2014-11-13 – 2014-11-15
• [Presentation] Effect of targeted overexpression of Foxe1 in a mouse thyroid (2014)
  • Author(s): A. Nikitski, N. Mitsutake, V. Saenko, T. Rogounovitch, S. Yamashita
  • Organizer: 第57回 日本甲状腺学会学術集会
  • Place of Presentation: ナレッジキャピタル コングレコンベンションセンター（大阪府大阪市）
  • Year and Date: 2014-11-13 – 2014-11-15
• [Presentation] Association of polymorphism in the FOXE1 gene locus with papillary thyroid carcinoma in Japanese patients (2014)
  • Author(s): V.Saenko, T.Rogounovitch, A.Bychkov, N.Mitsutake, M.Matsuse, E.Nishihara, M.Hirokawa, A.Nikitsky, S. Minami, K.Yamanouchi, K.Yoshiura, A.Miyauchi, S.Yamashita
  • Organizer: 第87回日本内分泌学会学術総会
  • Place of Presentation: 福岡国際会議場（福岡県 福岡市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] Rare T allele of rs944289 associates not only with risk of malignant but also of benign thyroid tumors (2014)
  • Author(s): Rogounovitch TI, Saenko VA, Bychkov A, Nikitski AV, Takahashi M, Nakashima M, Hayashi T, Hirokawa M, Miyauchi A, Ishigaki K, Shigematsu K, Matsuse M, Mitsutake N, Nishihara E, Minami S, Yamanouchi K , Ito M, Yoshiura K , Matsuda F, Yamashita S
  • Organizer: 第87回日本内分泌学会学術総会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] Identification of genes cooperating with mutant BRAF in thyroid (2013)
  • Author(s): ログノビッチ タチアナ, サエンコ ウラジミル, 光武範吏, ビチコフ アンドレイ,永山雄二,山下俊一
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台国際センター (仙台)
• [Presentation] Association of the NRG1 gene with risk for developing thyroid cancer after Chernobyl (2013)
  • Author(s): サエンコ ウラジミル,高橋めい子, ログノビッチ タチアナ, ドロズド ワレンチナ, デミドチク ユーリ, ボグダノワ タチアナ, トロンコ ミコラ, 光武範吏, 高村昇, 松田文彦 , 山下俊一
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台国際センター (仙台)
• [Presentation] MAY HIGH NITRATE LEVELS IN DRINKING WATER INCREASE THE PREVALENCE OF RADIATION-RELATED THYROID CANCER IN BELARUS? (2013)
  • Author(s): Drozd Valentina, Demidchik Yuri, Danilova Larisa, Kudelsky Alexander, Branovan Igor, Saenko Vladimir, Rogounovitch Tatiana, Yamashita Shunichi, Biko Johannes, Reiners Christoph
  • Organizer: 2nd World Congress on Thyroid Cancer
  • Place of Presentation: Toronto, Canada
• [Presentation] Rare allele of rs944289 (NKX2-1(TTF1)) associated with increasing risk of both malignant (PTC) and benign (FA) tumors in Japanese population (2013)
  • Author(s): Rogounovitch TI, Saenko VA, Bychkov A, Nikitski AV, Takahashi M, Nakashima M, Hayashi T, Hirokawa M, Miyauchi A, Shigematsu K, Mitsutake N, Matsuda F, Yamashita S
  • Organizer: European Thyroid Association 37th Annual Meeting
  • Place of Presentation: Leiden, The Netherlands
• [Presentation] Molecular epidemiology study of Chernobyl thyroid cancer from Belarus and Ukraine (2013)
  • Author(s): Vladimir Saenko, M.Takahashi, T.Rogounovitch, V.Drozd, Yu.Demidchik, T.Bogdanova, M.Tronko, N.Mitsutake, N.Takamura, F.Matsuda, S.Yamashita
  • Organizer: European Thyroid Association 37th Annual Meeting
  • Place of Presentation: Leiden, The Netherlands
• [Presentation] Genetic polymorphism on chromosome 14q13.3 associates with risk for thyroid follicular adenoma in Japanese patients (2013)
  • Author(s): ログノビッチ タチアナ, サエンコ ウラジミール, ビチコブ アンドレイ, ニキツキー アリャクサンドル, 高橋めい子, 中島正洋, 林徳眞吉, 廣川満良, 宮内昭, 石垣克, 重松和人, 光武範吏, 伊藤正博, 松田文彦, 山下俊一
  • Organizer: 第56回日本甲状腺学会学術集会
  • Place of Presentation: 和歌山県民文化会館 (和歌山市)
• [Presentation] Association of three polymorphisms of the FOXE1 gene with papillary thyroid carcinoma in Belarussian and Japanese populations (2013)
  • Author(s): サエンコ ウラジミル,高橋めい子, ログノビッチ タチアナ, ドロズド ワレンチナ, ビチコフ アンドレイ, 川口喬久, 光武範吏, 廣川満良, 西原永潤, 宮内昭, 吉浦孝一郎, 松田文彦, 山下俊一
  • Organizer: 第56回日本甲状腺学会学術集会
  • Place of Presentation: 和歌山県民文化会館 (和歌山市)
• [Presentation] Transcriptional activities of FOXE1 polyalanine tract variants (2013)
  • Author(s): ニキツキー アリャクサンドル,サエンコ ウラジミール, ビチコブ アンドレイ, ログノビッチ タチアナ, 光武範吏, 山下俊一
  • Organizer: 第56回日本甲状腺学会学術集会
  • Place of Presentation: 和歌山県民文化会館 (和歌山市)
• [Presentation] Patterns of FOXE1 expression in papillary thyroid carcinoma byImmunohistochemistry (2012)
  • Author(s): BychkovA, et al.
  • Organizer: 第53回原子爆弾後障害研究会
  • Place of Presentation: 長崎
  • Year and Date: 2012-06-03
• [Presentation] Differential expression of FOXE1 at tumor/host interface in papillarythyroid carcinoma (2012)
  • Author(s): BychkovA, et al.
  • Organizer: 第16回日本内分泌病理学会学術総会
  • Place of Presentation: 仙台
• [Presentation] Identification of genes cooperating with mutant BRAF in thyroid (2012)
  • Author(s): Rogounovitch T, et al.
  • Organizer: 10th Asia and Oceania Thyroid AssociationCongress
  • Place of Presentation: Kuta, Bali, Indonesia
• [Presentation] Clinical and genetic correlations of immunohistochemical FOXE1Expression in PTC in Japanese Patients (2012)
  • Author(s): BychkovA, et al.
  • Organizer: 10th Asia and Oceania Thyroid AssociationCongress
  • Place of Presentation: Kuta, Bali, Indonesia
• [Presentation] Identification of genes cooperating with BRAF in thyroid carcinogenesis (2012)
  • Author(s): ログノビツチ タチアナ
  • Organizer: 第55回日本甲状腺学会
  • Place of Presentation: 福岡
• [Presentation] Molecular epidemiology study of Chernobyl thyroid cancer inan extended sample set froom Belarus and Ukraine (2012)
  • Author(s): サエンコ ウラジミール
  • Organizer: 第55回日本甲状腺学会
  • Place of Presentation: 福岡
• [Presentation] Relationship of immunohistochemical FOXE1 expression to clinicalfeatures and genetic in PTC (2012)
  • Author(s): ビチコブ アンドレイ
  • Organizer: 第55回日本甲状腺学会
  • Place of Presentation: 福岡
• [Remarks] 長崎大学 原研医療
  • URL: http://www-sdc.med.nagasaki-u.ac.jp/drms/index.html
• [Remarks] 長崎大学 原爆後障害医療研究所 原研医療
  • URL: http://www-sdc.med.nagasaki-u.ac.jp/drms/
• [Remarks]
  • URL: http://www-sdc.med.nagasaki-u.ac.jp/drms/