Can TERT be a marker for prognosis and treatment decision making in thyroid cancer?

• Project/Area Number: 16K09804
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Nagasaki University
• Principal Investigator: MATSUSE Michiko 長崎大学, 原爆後障害医療研究所, 助教 (30533905)
• Co-Investigator(Kenkyū-buntansha): 光武 範吏 長崎大学, 原爆後障害医療研究所, 教授 (50404215)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 甲状腺癌 / TERT / 内分泌学

Outline of Final Research Achievements

The incidence of thyroid cancer has been increasing worldwide. Although most papillary thyroid carcinomas have a good prognosis, a small but certain fraction shows aggressive behavior. Therefore, a novel and well-performing molecular marker is needed.
In the present study, we examined whether mutations in the promoter region of the telomerase reverse transcriptase (TERT) gene could serve as a molecular marker as described above.
TERT promoter mutations were found to be useful as a prognostic molecular marker for thyroid cancer and were associated with resistance to radioiodine therapy. We also found that some TERT promoter mutation-negative cases expressed TERT mRNA, and those had a higher recurrence rate.

Academic Significance and Societal Importance of the Research Achievements

TERTプロモーター変異は甲状腺癌の予後予測分子マーカーとして有用であること、また放射性ヨード治療抵抗性と関連することを明らかにした。さらにTERT mRNAも甲状腺癌の新たな分子マーカーとして有用であることを明らかにした。このマーカーによって術前に癌の悪性度を予測できれば、手術を行う・行わない、半葉切除か全摘かなどの治療方針の決定に重要な情報を提供できる。これにより、治療・管理の最適化、患者QOLの改善、ひいては医療経済の節約にもつながるものと考える。

Research Products

• [Journal Article] TERT mRNA Expression as a Novel Prognostic Marker in Papillary Thyroid Carcinomas (2019)
  • 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
  • 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
  • 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 cells (2019)
  • 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
  • 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
  • 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’ Disease (2018)
  • 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
  • Peer Reviewed
• [Journal Article] Sporadic pediatric papillary thyroid carcinoma harboring the ETV6/NTRK3 fusion oncogene in a 7-year-old Japanese girl: a case report and review of literature. (2018)
  • Author(s): Otsubo R, Mussazhanova Z, Akazawa Y, Sato A, Matsuda K, Matsumoto M, Yano H, Matsuse M, Mitsutake N, Ando T, Niino D, Nagayasu T, Nakashima M.
  • Journal Title: Endocrinol Metab Volume: 31 Issue: 4 Pages: 461-467
  • DOI: 10.1515/jpem-2017-0292
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] TERT Promoter Mutations Were Not Found in Papillary Thyroid Microcarcinomas That Showed Disease Progression on Active Surveillance. (2017)
  • Author(s): Yabuta T, Matsuse M, Hirokawa M, Yamashita S, Mitsutake N, Miyauchi A.
  • Journal Title: Thyroid Volume: 27(9) Issue: 9 Pages: 1206-1207
  • DOI: 10.1089/thy.2016.0645
  • Peer Reviewed
• [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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TERT promoter mutations and Ki-67 labeling index as a prognostic marker of papillary thyroid carcinomas: combination of two independent factors. (2017)
  • Author(s): Matsuse M, Yabuta T, Saenko V, Hirokawa M, Nishihara E, Suzuki K, Yamashita S, Miyauchi A, Mitsutake N.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 41752-41752
  • DOI: 10.1038/srep41752
  • NAID: 120006987562
  • Peer Reviewed / Open Access
• [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
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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
• [Presentation] 甲状腺乳頭癌におけるTERTプロモーター変異のアレル頻度・TERT mRNA発現と予後との関連性について (2018)
  • Author(s): 田中彩、松瀬美智子、光武範吏
  • Organizer: 2.第61回日本甲状腺学会学術集会
• [Presentation] 甲状腺癌幹細胞に重要なシグナル伝達経路の解析 (2017)
  • Author(s): 松瀬 美智子
  • Organizer: 第60回日本甲状腺学会学術集会
• [Presentation] 定量RT-PCR法を用いた融合遺伝子スクリーニングにより同定した甲状腺癌新規融合遺伝子の機能解析 (2016)
  • Author(s): 松瀬 美智子
  • 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