Pathogenic significance of TERT promoter mutation in progression of thyroid cancer

• Project/Area Number: 15K19050
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: University of Yamanashi
• Principal Investigator: OISHI Naoki 山梨大学, 総合研究部, 助教 (90623661)
• Research Collaborator: KONDO Tetsuo ; EBINA Aya ; SATO Yukiko ; AKAISHI Junko ; HINO Rumi ; YAMAMOTO Noriko ; YOKOMICHI Hiroshi ; MOCHIZUKI Kunio ; NAKAZAWA Tadao ; ITO Koichi ; YABUTA Tomonori ; HIROKAWA Mitsuyoshi ; MIYAUCHI Akira ; ISHIKAWA Yuichi ; KATOH Ryohei
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 甲状腺癌 / 未分化癌 / 乳頭癌 / 未分化転化 / TERT / BRAF / PIK3CA / SWI/SNF / 遺伝子異常

Outline of Final Research Achievements

We examined genetic alterations in coexisting thyroid papillary carcinoma (PC) and anaplastic carcinoma (AC) to elucidate risk factors for anaplastic transformation. In the series of PC-derived ACs, BRAF and TERT promoter mutations were the most frequent alternations. These two mutations occurred prior to anaplastic transformation. Furthermore, using multivariate analysis with control PCs, we identified TERT promoter mutation to be an independent risk factor for anaplastic transformation. We also demonstrated PIK3CA mutations and aberrant expression of p53, TTF-1 and SWI/SNF proteins in a subset of PC-derived AC with temporally heterogeneous pattern of acquisition. By showing that TERT is highly associated with anaplastic transformation, it opens the possibility of stratifying PC patients for therapy using TERT promoter mutations.

Research Products

• [Journal Article] Prognostic significance of diffuse sclerosing variant papillary thyroid carcinoma: a systematic review and meta-analysis. (2017)
  • Author(s): Vuong HG, Kondo T, Pham TQ, Oishi N, Mochizuki K, Nakazawa T, Hassell L, Katoh R.
  • Journal Title: Eur J Endocrinol. Volume: 176(4) Issue: 4 Pages: 431-439
  • DOI: 10.1530/eje-16-0863
  • Peer Reviewed
• [Journal Article] Frequent BRAF (V600E) and Absence of TERT Promoter Mutations Characterize Sporadic Pediatric Papillary Thyroid Carcinomas in Japan. (2017)
  • Author(s): Oishi N, Kondo T, Nakazawa T, Mochizuki K, Inoue T, Kasai K, Tahara I, Yabuta T, Hirokawa M, Miyauchi A, Katoh R.
  • Journal Title: Endocr Pathol. Volume: 未定 Issue: 2 Pages: 103-111
  • DOI: 10.1007/s12022-017-9470-y
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The changing characteristics and molecular profiles of papillary thyroid carcinoma over time: a systematic review. (2017)
  • Author(s): Vuong HG, Altibi AM, Abdelhamid AH, Ngoc PU, Quan VD, Tantawi MY, Elfil M, Vu TL, Elgebaly A, Oishi N, Nakazawa T, Hirayama K, Katoh R, Huy NT, Kondo T.
  • Journal Title: Oncotarget. Volume: 8(6) Issue: 6 Pages: 10637-10649
  • DOI: 10.18632/oncotarget.12885
  • Peer Reviewed / Open Access
• [Journal Article] Genetic alterations of differentiated thyroid carcinoma in iodine-rich and iodine-deficient countries. (2016)
  • Author(s): Vuong HG, Kondo T, Oishi N, Nakazawa T, Mochizuki K, Inoue T, Tahara I, Kasai K, Hirokawa M, Tran TM, Katoh R.
  • Journal Title: Cancer Med. Volume: 5(8) Issue: 8 Pages: 1883-1889
  • DOI: 10.1002/cam4.781
  • Peer Reviewed
• [Journal Article] Extranodal NK/T-cell lymphoma, nasal type of the uterine cervix: A case report. (2016)
  • Author(s): Omori M, Oishi N, Nakazawa T, Nakazawa K, Mitsumori T, Yuminamochi T, Kirito K, Hirata S.
  • Journal Title: Diagn Cytopathol. Volume: 44(5) Issue: 5 Pages: 430-433
  • DOI: 10.1002/dc.23439
  • Peer Reviewed
• [Journal Article] Immunohistochemical Detection of NRASQ61R Protein in Follicular-patterned Thyroid Tumors. (2016)
  • Author(s): Oishi N, Kondo T, Vuong HG, Nakazawa T, Mochizuki K, Kasai K, Inoue T, Tahara I, Hirokawa M, Miyauchi A, Katoh R.
  • Journal Title: Hum Pathol. Epub ahead of print Volume: - Pages: 51-57
  • DOI: 10.1016/j.humpath.2016.02.008
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 単房性嚢胞を形成した膵神経内分泌腫瘍の1例 (2016)
  • Author(s): 井上朋大, 近藤哲夫, 望月邦夫, 大石直輝, 河西一成, 田原一平, 中澤匡男, 板倉淳, 藤井秀樹, 加藤良平
  • Journal Title: 診断病理 Volume: 33 Pages: 246-249
  • Peer Reviewed
• [Journal Article] 【第7版の甲状腺癌取扱い規約における変更点について】 甲状腺乳頭癌の特殊型 (2016)
  • Author(s): 大石直輝, 近藤哲夫
  • Journal Title: 日本内分泌・甲状腺外科学会雑誌 Volume: 33 Pages: 73-77
• [Journal Article] Spindle cell oncocytoma of adenohypophysis: Report of a case and immunohistochemical review of literature. (2016)
  • Author(s): Vuong HG, Kondo T, Tran TM, Oishi N, Nakazawa T, Mochizuki K, Inoue T, Kasai K, Tahara I, Jieying W, Katoh R.
  • Journal Title: Pathol Res Pract. Volume: 212 Issue: 3 Pages: 222-225
  • DOI: 10.1016/j.prp.2015.07.014
  • Peer Reviewed / Open Access
• [Journal Article] Branchial Cleft-Like Cysts Involving 3 Different Organs: Thyroid Gland, Thymus, and Parotid Gland. (2015)
  • Author(s): Nakazawa T, Kondo T, Oishi N, Tahara I, Kasai K, Inoue T, Mochizuki K, Katoh R.
  • Journal Title: Medicine Volume: 94 Issue: 42 Pages: e1758-e1758
  • DOI: 10.1097/md.0000000000001758
  • Peer Reviewed / Open Access
• [Journal Article] High prevalence of the MYD88 mutation in testicular lymphoma: Immunohistochemical and genetic analyses. (2015)
  • Author(s): Oishi N, Kondo T, Nakazawa T, Mochizuki K, Tanioka F, Oyama T, Yamamoto T, Iizuka J, Tanabe K, Shibata N, Kirito K, Katoh R.
  • Journal Title: Pathol Int. Volume: 65 Issue: 10 Pages: 528-535
  • DOI: 10.1111/pin.12336
  • Peer Reviewed / Open Access
• [Presentation] 乳頭癌における TERT 変異は未分化転化のリスクである -未分化転化をきたした 乳頭癌の分子病理学的解析- (2016)
  • Author(s): 大石直輝 ほか
  • Organizer: 第20回日本内分泌病理学会
  • Place of Presentation: 東京都・板橋区
  • Year and Date: 2016-09-16
• [Presentation] Immunohistochemical detection of NRASQ61R protein in Follicular-patterned Thyroid Tumors (2016)
  • Author(s): 大石直輝 ほか
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 宮城県・仙台市
  • Year and Date: 2016-05-12
• [Presentation] 甲状腺癌におけるsialyl lewis a、sialyl lewis x の発現 (2016)
  • Author(s): 河西一成、加藤良平、近藤哲夫、中澤匡男、望月邦夫、 大石直輝、井上朋大、田原一平
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター (宮城県仙台市)
  • Year and Date: 2016-05-12
• [Presentation] 甲状腺乳頭癌核の多次元的構造解析 -連続ブロック表面走査型電子顕微鏡 （SBF-SEM）を用いて- (2016)
  • Author(s): 井上朋大、大野伸彦、田原一平、河西一成、大石直輝、 望月邦夫、中澤匡男、近藤哲夫、加藤良平
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター (宮城県仙台市)
  • Year and Date: 2016-05-12
• [Presentation] 甲状腺がん微小環境における細胞外アデノシン、アデノシン受容体の腫瘍促進作用 (2016)
  • Author(s): 近藤哲夫、中澤匡男、大石直輝、望月邦夫、加藤良平
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター (宮城県仙台市)
  • Year and Date: 2016-05-12
• [Presentation] Immunohistochemical detection of NRASQ61R protein in Follicular-patterned Thyroid Tumors (2016)
  • Author(s): 大石直輝、近藤哲夫、Gia Huy Vuong、中澤匡男、望月邦夫、 河西一成、井上朋大、田原一平、廣川満良、加藤良平
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター (宮城県仙台市)
  • Year and Date: 2016-05-12
• [Presentation] Immunohistochemical Detection of NRASQ61R Protein in Follicular-Patterned Thyroid Tumors (2016)
  • Author(s): Naoki Oishi, Tetsuo Kondo, Huy Vuong, Tadao Nakazawa, Kunio Mochizuki, Kazunari Kasai, Tomohiro Inoue, Ippei Tahara, Mitsuyoshi Hirokawa, Akira Miyauchi, Ryohei Katoh
  • Organizer: The United States and Canadian Academy of Pathology
  • Place of Presentation: Seattle (USA)
  • Year and Date: 2016-03-12
  • Int'l Joint Research
• [Presentation] 連続ブロック表面走査型顕微鏡(SBF-SEM)による甲状腺乳頭癌細胞核の3次元イメージ解析 (2015)
  • Author(s): 井上 朋大, 大野 伸彦, 田原 一平, 河西 一成, 大石 直輝, 望月 邦夫, 中澤 匡男, 近藤 哲夫, 村田 和義, 加藤 良平
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場 (愛知県名古屋市)
  • Year and Date: 2015-04-30
• [Presentation] 甲状腺乳頭癌における血管浸潤像の評価とその臨床病理学的意義 (2015)
  • Author(s): 河西 一成, 田原 一平, 井上 朋大, 大石 直輝, 望月 邦夫, 中澤 匡男, 近藤 哲夫, 加藤 良平
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場名古屋国際会議場 (愛知県名古屋市)
  • Year and Date: 2015-04-30
• [Presentation] 甲状腺癌における低分化成分の臨床的意義 (2015)
  • Author(s): 近藤 哲夫, 赤石 純子, 中澤 匡男, 大石 直輝, 田原 一平, 河西 一成, 井上 朋大, 望月 邦夫, 伊藤 公一, 加藤 良平
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場 (愛知県名古屋市)
  • Year and Date: 2015-04-30
• [Presentation] 大石 直輝, 近藤 哲夫, 中澤 匡男, 望月 邦夫, 薮田 智範, 廣川 満良, 宮内 昭, 加藤 良平 (2015)
  • Author(s): 小児・若年甲状腺乳頭癌におけるBRAFV600E変異とTERTプロモーター変異の解析
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場 (愛知県名古屋市)
  • Year and Date: 2015-04-30
• [Remarks] 研究 山梨大学医学部人体病理学講座
  • URL: http://www.med.yamanashi.ac.jp/clinical_basic/pathol02/research.html