Whole exome sequencing ot intraductal tubulopapillary neoplasm of the pancreas

• Project/Area Number: 26460458
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Tokyo Medical University (2015-2016); Saitama Medical University (2014)
• Principal Investigator: Yamaguchi Hiroshi 東京医科大学, 医学部, 准教授 (20510697)
• Co-Investigator(Kenkyū-buntansha): 古川 徹 東京女子医科大学, 医学部, 教授 (30282122)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 膵癌 / 膵管内腫瘍 / 全エクソン解析 / DNA解析 / 次世代シーケンサー

Outline of Final Research Achievements

Intraductal tubulopapillary neoplasm (ITPN) of the pancreas, proposed by us in 2009, is a lately established new disease entity among pancreatic carcinomas. The genetic alterations involved in the carcinogenesis of ITPN has been supposed to be different from other pancreatic neoplasms, However, data on the genetic features of ITPN are fairly limited, partially due to the rarity of the neoplasm. By comprehensive genetic analyses including whole-exome sequencing and targeted cancer gene panel sequencing, we detected several genetic alterations in ITPNs, such as somatic mutations of PIK3CA, which are obviously different from other pancreatic neoplasms. The results support the independence of ITPN as a single disease entity. In addition, the newly uncovered genetic alterations will lead to a novel diagnostic and therapeutic strategies.

Research Products

• [Int'l Joint Research] Memorial Sloan Kettering Cancer Center(米国)
• [Journal Article] Pancreatic intraductal tubulopapillary neoplasm is genetically distinct from intraductal papillary mucinous neoplasm and ductal adenocarcinoma (2017)
  • Author(s): Olca Basturk, Michael Berger, Hiroshi Yamaguchi et al.
  • Journal Title: Modern Pathology Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A case of intraductal papillary neoplasm of the bile duct preoperatively diagnosed using contrast-enhanced endoscopic ultrasonography (2016)
  • Author(s): Tanisaka Y1, Iwano H, Taba K, Sato H, Harada M, Katsukura N, Aikawa K, Miyazawa M, Yamaguchi H, Ryozawa S.
  • Journal Title: Nippon Shokakibyo Gakkai Zasshi Volume: 113 Issue: 7 Pages: 1236-1243
  • DOI: 10.11405/nisshoshi.113.1236
  • NAID: 130005162979
  • ISSN: 0446-6586, 1349-7693
  • Peer Reviewed
• [Journal Article] 6年3ヵ月という長期間に及ぶ自然史を画像経過で観察できた胃穿破を伴う分枝型IPMN由来浸潤癌の1例 (2016)
  • Author(s): 山本 健治郎, 糸井 隆夫, 祖父尼 淳, 土屋 貴愛, 辻 修二郎, 池内 信人, 鎌田 健太郎, 田中 麗奈, 殿塚 亮祐, 本定 三季, 向井 俊太郎, 藤田 充, 山口 浩, 永川 裕一, 土田 明彦
  • Journal Title: 膵臓 Volume: 31 Pages: 728-737
  • Peer Reviewed
• [Journal Article] A case of small solid-pseudopapillary neoplasm (SPN) in a male preoperatively diagnosed by twice use of EUS-FNA (2016)
  • Author(s): 谷坂 優樹, 岩野 博俊, 田場 久美子, 佐藤 洋子, 原田 舞子, 勝倉 暢洋, 岡田 克也, 宮澤 光男, 山口 浩, 須藤 晃佑, 新井 晋, 真下 由美, 良沢 昭銘
  • Journal Title: Suizo Volume: 31 Issue: 1 Pages: 101-108
  • DOI: 10.2958/suizo.31.101
  • NAID: 130005137835
  • ISSN: 0913-0071, 1881-2805
  • Peer Reviewed
• [Journal Article] Malignant Progression of Mixed Type IPMN Which Formed a Duodenum Fistula during Long-term Observation (2015)
  • Author(s): 渡邉 幸博, 岡本 光順, 森田 洋平, 石田 慎悟, 岡田 克也, 合川 公康, 宮澤 光男, 小山 勇, 山口 浩, 清水 道生
  • Journal Title: The Japanese Journal of Gastroenterological Surgery Volume: 48 Issue: 9 Pages: 769-775
  • DOI: 10.5833/jjgs.2014.0201
  • NAID: 130005099693
  • ISSN: 0386-9768, 1348-9372
  • Peer Reviewed
• [Journal Article] Whole exome sequencing reveals recurrent mutations in BRCA2 and FAT genes in acinar cell carcinomas of the pancreas. (2015)
  • Author(s): Furukawa T, Sakamoto H, Takeuchi S, Mitra A, Kuboki Y, Yamamoto T, Hatori T, Yamamoto M, Sugiyama M, Ohike N, Yamaguchi H, Shimizu M, Shibata N, Shimizu K, Shiratori K.
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 8829-8829
  • DOI: 10.1038/srep08829
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Intraductal tubulopapillary neoplasm, a novel precursor of invasive carcinoma of the pancreas (2016)
  • Author(s): Hiroshi Yamaguchi, Toshitaka Nagao
  • Organizer: Joint Conference of the International Association of Pancreatology (IAP), the Japan Pancreas Society (JPS) and the Asian- Oceanic Pancreatic Association (AOPA)
  • Place of Presentation: Sendai International Center, Sendai
  • Year and Date: 2016-08-05
  • Int'l Joint Research
• [Presentation] Intraductal tubulopapillary neoplasmの病理学的特徴とその鑑別疾患 (2016)
  • Author(s): 山口 浩
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台国際センター・仙台
  • Year and Date: 2016-05-12
• [Presentation] 膵腺房細胞癌2例の細胞学的特徴像 (2015)
  • Author(s): 片桐仁子，山口浩，大城久，小池悦子，三宅真司，桑原淳，磯本愛子，鈴木恵美子，大塚清花，忽滑谷昌平，松林純，長尾俊孝
  • Organizer: 第54回日本臨床細胞学会秋期大会
  • Place of Presentation: 名古屋国際会議場・名古屋
  • Year and Date: 2015-11-21
• [Presentation] 膵intraductal tubulopapillary neoplasm - WHO 分類基準改定に至った新規腫瘍概念 - (2015)
  • Author(s): 山口浩
  • Organizer: 第61回日本病理学会秋期特別総会
  • Place of Presentation: 東京大学・東京
  • Year and Date: 2015-11-05
  • Invited
• [Presentation] 膵 Solid-pseudopapillary neoplasm (2015)
  • Author(s): 山口浩
  • 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
  • Year and Date: 2015-04-30
  • Invited
• [Presentation] Histological Invasive Patterns of Intraductal Tubulopapillary Neoplasms of the Pancreas. (2014)
  • Author(s): H. Yamaguchi, M. Shimizu, I. Koyama, T Hatori, M. Yamamoto, K. Shimizu, K. Shiratori, T. Furukawa
  • Organizer: American Pancreatic Association/Japan Pancreas Society 45th Anniversary Meeting
  • Place of Presentation: Hapuna Beach Prince Resort, Big Island, Hawaii
  • Year and Date: 2014-11-05 – 2014-11-08
• [Presentation] 膵腫瘍類似病変 -過誤腫・扁平上皮性嚢胞を中心に- (2014)
  • Author(s): 山口浩，清水道生
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島国際会議場・広島
  • Year and Date: 2014-04-24 – 2014-04-26
  • Invited