SGO1 mutation by MSI induces CIN

• Project/Area Number: 16K09305
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Iwaizumi Moriya 浜松医科大学, 医学部, 助教 (60444361)
• Co-Investigator(Kenkyū-buntansha): 華表 友暁 浜松医科大学, 医学部, 助教 (40416665)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 染色体不安定性 / マイクロサテライト不安定性 / 胃がん / 大腸癌 / SGO1 / 大腸がん

Outline of Final Research Achievements

We demonstrated that 1)SGO1 gene has five microsatellite instability regions 2)among five MS regions we found that one region had somatic mutation in high frequency in gastric cancer and colorectal cancer. 3)We established the truncated SGO1 protein expression vector lead by the mutation.

Academic Significance and Societal Importance of the Research Achievements

本研究により、マイクロサテライト領域のフレームシフト変異は必ずしもマイクロサテライト不安定性に依存するとは限らないということが判明した。すなわち現在免疫チェックポイント阻害薬の標的であろうとされるTumor mutation burdenが必ずしもマイクロサテライト不安定性によるものではないのと同様、他に変異を起こしやすい原因があることを示唆する。

Research Products

• [Int'l Joint Research] ミシガン大学(米国)
• [Journal Article] <i>MBD4</i> frameshift mutation caused by DNA mismatch repair deficiency enhances cytotoxicity by trifluridine, an active antitumor agent of TAS-102, in colorectal cancer cells (2017)
  • Author(s): Suzuki Satoshi、Iwaizumi Moriya、Yamada Hidetaka、Sugiyama Tomohiro、Hamaya Yasushi、Furuta Takahisa、Kanaoka Shigeru、Sugimura Haruhiko、Miyajima Hiroaki、Osawa Satoshi、Carethers John M.、Sugimoto Ken
  • Journal Title: Oncotarget Volume: 9 Issue: 14 Pages: 11477-11488
  • DOI: 10.18632/oncotarget.22484
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Production of truncated MBD4 protein by frameshift mutation in DNA mismatch repair-deficient cells enhances 5-fluorouracil sensitivity that is independent of hMLH1 status. (2016)
  • Author(s): Satoshi Suzuki, Ken Sugimoto, et al.
  • Journal Title: Cancer Biol Ther Volume: 17 Issue: 7 Pages: 760-768
  • DOI: 10.1080/15384047.2016.1178430
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 遺伝性腫瘍研究・腫瘍各論 家族性胃がん (2016)
  • Author(s): 岩泉守哉、椙村春彦
  • Journal Title: 遺伝子医学MOOK 別冊（最新遺伝性腫瘍・家族性腫瘍研究と遺伝カウンセリング） Volume: 別冊 Pages: 202-206
• [Presentation] A frameshift mutation of SGO1 independent of MSI-H/dMMR has a potential of resistance for taxane in gastric cancer. (2019)
  • Author(s): Tomohiro Sugiyama, Moriya Iwaizumi, Satoshi Suzuki, Ken Sugimoto, Masato Maekawa, Haruhiko Sugimura
  • Organizer: 11th AACR-JCA Joint Conference on Breakthroughs in Cancer Research: Biology to Precision Medicine
  • Int'l Joint Research
• [Presentation] FAP患者における胃癌の検討－遺伝的要因が胃癌診療で重要視される時代へ－ (2016)
  • Author(s): 岩泉守哉、山田英孝、椙村春彦
  • Organizer: 第24回日本消化器関連学会週間 (JDDW2016)
  • Place of Presentation: 神戸
  • Year and Date: 2016-11-03
• [Presentation] 孤発性家族性大腸腺腫症はAPC短縮変異により引き起こされやすい (2016)
  • Author(s): 岩泉守哉、陶弘、杉山智洋、濱屋寧、倉地清隆、古川洋一、前川真人、椙村春彦
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] 「大腸がんのプライマリケア遺伝診療」のための家庭医療スタッフの関わり (2016)
  • Author(s): 岩泉守哉、鳴本敬一郎、福江美咲、倉地清隆、椙村春彦、前川真人、緒方勤、井上真知子
  • Organizer: 第22回日本家族性腫瘍学会学術集会
  • Place of Presentation: 松山
  • Year and Date: 2016-06-03