Investigation of genetic alterations of mucin-depleted foci in patients with sporadic colorectal cancer

• Project/Area Number: 24790713
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Yokohama City University
• Principal Investigator: SAKAI Eiji 横浜市立大学, 附属病院, 指導診療医 (30600233)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: MDF / 前がん病変 / 大腸発癌 / ACF / 遺伝子変異 / メチル化異常 / mucin-depleted foci / de novo pathway / 大腸発がん / DNAメチル化

Research Abstract

Mucin-depleted foci (MDF), formed by dysplastic crypts devoid of mucin production have been recognized to be correlated with colorectal carcinogenesis and to serve as preneoplastic lesions of colorectal cancer (CRC). In the present study, we investigated the genetic and epigenetic alterations of MDF to reveal carcinogenic mechanisms of these lesions. A part of MDF showed aberrant beta-catenin accumulation as well as flat-neoplasms, suggesting that these lesions might be served as precursor of CRC which develop through de novo pathway. However, we could not analyze detail genetic and epigenetic alterations, because of low quality and quantity of DNA. In the future, endoscopic detection may be help to reveal carcinogenic mechanisms of MDF development.

Research Products

• [Journal Article] Methylation epigenotypes and genetic features in colorectal laterally spreading tumors (2014)
  • Author(s): Sakai E, Ohata K, Chiba H, Matsuhashi N, Doi N, Fukushima J, Endo H, Takahashi H, Tsuji S, Yagi K, Matsusaka K, Aburatani H, Nakajima A, Kaneda A.
  • Journal Title: Int J Cancer Volume: in press Issue: 7 Pages: 1586-95
  • DOI: 10.1002/ijc.28814
  • Peer Reviewed / Open Access
• [Journal Article] Accumulation of aberrant DNA methylation during colorectal cancer development (2014)
  • Author(s): Sakai E, Nakajima A, Kaneda A.
  • Journal Title: World J Gastroenterol Volume: 28; 20(4) Issue: 4 Pages: 978-87
  • DOI: 10.3748/wjg.v20.i4.978
  • Peer Reviewed
• [Journal Article] Methylation epigenotypes and genetic features in colorectal laterally spreading tumors. (2014)
  • Author(s): Sakai E, Ohata K, Chiba H, Matsuhashi N, Doi N, Fukushima J, Endo H, Takahashi H, Tsuji S, Yagi K, Matsusaka K, Aburatani H, Nakajima A, Kaneda A.
  • Journal Title: Int J Cancer. Volume: in print
  • Peer Reviewed
• [Journal Article] Accumulation of aberrant DNA methylation during colorectal cancer development. (2014)
  • Author(s): Sakai E, Nakajima A, Kaneda A.
  • Journal Title: World J Gastroenterol. Volume: 28 (20) Pages: 978-87
  • Peer Reviewed
• [Presentation] The characteristics of genetic and epigenetic alterations in laterally spreading colorectal tumors. (2013)
  • Author(s): Sakai E, Ohata K, Chiba H, Matsuhashi N, Fukushima J, Endo H, Takahashi H, Aburatani H, Nakajima A, Kaneda A.
  • Organizer: UEGW annual meeting
  • Place of Presentation: ICC Berlin
  • Year and Date: 2013-10-15
• [Presentation] The genetic alterations and unique epigenotype of laterally spreading colorectal tumors (2013)
  • Author(s): Sakai E, Ohata K, Chiba H, Matsuhashi N, Fukushima J, Endo H, Takahashi H, Aburatani H, Nakajima A, Kaneda A.
  • Organizer: 第72回日本癌学会総会
  • Place of Presentation: パシフィコ横浜(口演発表)
  • Year and Date: 2013-10-05
• [Presentation] The characteristics of genetic and epigenetic alterations in laterally spreading colorectal tumors. (2013)
  • Author(s): Sakai E, Ohata K, Chiba H, Matsuhashi N, Fukushima J, Endo H, Takahashi H, Aburatani H, Nakajima A, Kaneda A.
  • Organizer: UEGW annual meeting
  • Place of Presentation: ドイツ ベルリン
• [Presentation] The genetic alterations and unique epigenotype of laterally spreading colorectal tumors. (2013)
  • Author(s): Sakai E, Ohata K, Chiba H, Matsuhashi N, Fukushima J, Endo H, Takahashi H, Aburatani H, Nakajima A, Kaneda A.
  • Organizer: 第72回日本癌学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] Low dose resveratrol do not inhibit colorectal tumor initiation but progression via suppression of STAT3 signal (2012)
  • Author(s): 酒井英嗣
  • Organizer: 第71回 日本癌学会
  • Place of Presentation: ホテルロイトン札幌（札幌）
• [Presentation] The histopathological characteristics of mucin-depleted foci in patients with sporadic colorectal cancer. (2012)
  • Author(s): Eiji Sakai
  • Organizer: AACR annual meeting 2012
  • Place of Presentation: Chikago, USA
• [Presentation] Capsule endoscopy with flexible spectral imaging color enhancement reduces the bile-pigments effect and improves the detectability of small bowel lesions. (2012)
  • Author(s): Eiji Sakai
  • Organizer: DDW 2012
  • Place of Presentation: San Diego, USA