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Molecular markers that can predict highly malignant papillary thyroid cancer

Research Project

Project/Area Number 19K09913
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionNagasaki University

Principal Investigator

Matsuse Michiko  長崎大学, 原爆後障害医療研究所, 助教 (30533905)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords甲状腺癌 / TERT
Outline of Research at the Start

甲状腺癌は悪性度に関して広い性質を持ち、癌が小さなものから進行する際に、ある段階で留まるものや、増悪していくものがある。これまで申請者らはKi-67発現やTERTプロモーター変異が甲状腺癌の悪性度を予測できることを報告したが、臨床応用するためには未だ様々な問題点がある。よって本研究では、穿刺吸引細胞診検体を用いた臨床応用を念頭に置き、上記の問題点を解決することを目的とする。術前細胞診検体で悪性度を予測できる分子マーカーを確立することによって、最適な治療方針選択を可能とし、患者QOLの向上に貢献、さらには新たな治療ターゲットの同定に繋げる。

Outline of Final Research Achievements

The incidence of papillary thyroid carcinoma (PTC) has been increasing worldwide. Although most PTCs have a favorable prognosis, small but certain fraction show aggressive behavior. Therefore, a novel and well-performing molecular marker is needed.
In the present study, we developed a highly sensitive detection method for TERT promoter (TERT-p) mutations. Using our method, we could detect TERT-p mutations even from a small amount of DNA samples and showed that the detection of this mutations using preoperative samples could be clinically useful. We also found that TERT-p mutations and TERT mRNA expression can be useful prognostic markers in elderly and young PTC patients, respectively.

Academic Significance and Societal Importance of the Research Achievements

TERTは甲状腺癌のみならず膀胱癌、肝癌、黒色腫、脳腫瘍をはじめ様々な癌で悪性度と関連しているとされ、本研究によって得られた知見は、他癌種にも応用可能である。また、術前細胞診検体で悪性度を予測できる分子マーカーを確立することによって、最適な治療方針選択を可能とし、患者QOLの向上、医療経済にも貢献できる。近年、スプライシングを制御する薬剤が同定されてきているが、本研究の成果によってこの種の薬剤が抗がん剤として開発が進む可能性もある。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (12 results)

All 2021 2020 2019 2018 Other

All Journal Article (7 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (4 results) (of which Invited: 1 results) Remarks (1 results)

  • [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.
    • Journal Title

      Clinical Endocrinology

      Volume: 95 Issue: 5 Pages: 790-799

    • DOI

      10.1111/cen.14567

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [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
    • Journal Title

      J Clin Endocrinol Metab

      Volume: 105 Issue: 12 Pages: 573-573

    • DOI

      10.1210/clinem/dgaa573

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TERT mRNA Expression as a Novel Prognostic Marker in Papillary Thyroid Carcinomas2019

    • Author(s)
      Tanaka Aya、Matsuse Michiko、Saenko Vladimir、Nakao Tomoe、Yamanouchi Kosho、Sakimura Chika、Yano Hiroshi、Nishihara Eijun、Hirokawa Mitsuyoshi、Suzuki Keiji、Miyauchi Akira、Eguchi Susumu、Yoshiura Ko-ichiro、Yamashita Shunichi、Nagayasu Takeshi、Mitsutake Norisato
    • Journal Title

      Thyroid

      Volume: 29 Issue: 8 Pages: 1105-1114

    • DOI

      10.1089/thy.2018.0695

    • NAID

      120006988431

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] TERT promoter mutation in primary papillary thyroid carcinoma lesions predicts absent or lower 131I uptake in metastases.2019

    • Author(s)
      Meng Z, Matsuse M, Saenko V, Yamashita S, Ren P, Zheng X, Jia Q, Tan J, Li N, Zheng W, Zhao L, Mitsutake N.
    • Journal Title

      IUBMB Life.

      Volume: 71 Issue: 7 Pages: 10301040-10301040

    • DOI

      10.1002/iub.2056

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The JAK/STAT3 and NF-kappa B signaling pathways regulate cancer stem cell properties in anaplastic thyroid cancer cells2019

    • Author(s)
      K. Shiraiwa, M. Mitsutake, Y. Nakazawa, T. Ogi, K. Suzuki, V. Saenko, K. Umezawa, S. Yamashita, K. Tsukamoto
    • Journal Title

      Thyroid

      Volume: in press Issue: 5 Pages: 674-682

    • DOI

      10.1089/thy.2018.0212

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / 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
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rapid Growth and Early Metastasis of Papillary Thyroid Carcinoma in an Adolescent Girl with Graves’ Disease2018

    • Author(s)
      Shimura Kazuhiro、Shibata Hironori、Mizuno Yusuke、Amano Naoko、Hoshino Ken、Kuroda Tatsuo、Kameyama Kaori、Matsuse Michiko、Mitsutake Norisato、Sugino Kiminori、Yoshimura?Noh Jaeduk、Hasegawa Tomonobu、Ishii Tomohiro
    • Journal Title

      Hormone Research in Paediatrics

      Volume: - Issue: 3 Pages: 1-6

    • DOI

      10.1159/000491102

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] TERTの転写制御の違いと甲状腺癌悪性度との関連2021

    • Author(s)
      松瀬美智子、酒匂あやか、Vladimir Saenko、山下俊一、光武範吏
    • Organizer
      第64回日本甲状腺学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 甲状腺乳頭癌におけるTERT mRNAのスプライシングバリアントとTERTプロモーター変異・臨床病理学的指標との関連2021

    • Author(s)
      酒匂あやか 、松瀬美智子、サエンコ ウラジミール、西原永潤、廣川満良、宮内昭、川上純、光武範吏
    • Organizer
      第64回日本甲状腺学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 増悪する甲状腺乳頭癌を予測できる分子マーカー:さらなる高精度化と細胞診への応用2020

    • Author(s)
      松瀬美智子、中尾朋恵、光武範吏
    • Organizer
      第63回日本甲状腺学会学術集会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 甲状腺乳頭癌におけるTERTプロモーター領域のメチル化とmRNA発現の検討2019

    • Author(s)
      松瀬美智子、光武範吏
    • Organizer
      第62回日本甲状腺学会学術集会
    • Related Report
      2019 Research-status Report
  • [Remarks] 原研医療ホームページ

    • URL

      https://www.genken.nagasaki-u.ac.jp/drms/

    • Related Report
      2021 Annual Research Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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