Elucidation of molecular pathology and development of diagnostic and therapeutic methods in poorly differentiated colorectal adenocarcinoma by integrated genome and epigenome analysis

• Project/Area Number: 15K19339
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: Aoki Hironori 札幌医科大学, 医学部, 研究員 (40749496)
• Co-Investigator(Renkei-kenkyūsha): SUZUKI Hiromu 札幌医科大学, 医学部, 教授 (20381254) ; YAMAMOTO Eiichiro 札幌医科大学, 医学部, 助教 (60567915)
• Research Collaborator: YAMANO Hiro-o ; SUGAI Tamotsu
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 大腸低分化腺癌 / 大腸鋸歯状病変 / 大腸腫瘍

Outline of Final Research Achievements

We performed extraction of DNA and RNA using colorectal tumor tissues which were endoscopically and surgically resected. Next we performed RNA sequencing using extracted RNA, and we identified several genes which expressed in early invasive colorectal cancers with poorly differentiated adenocarcinomas.
We carried out Infinium HumanMethylation 450 BeadChip analysis using extracted DNA. BeadChip analysis revealed gene A in which methylation levels were progressively increased during development of traditional serrated adenomas (TSAs). Methylation analysis of many colorectal lesions by pyrosequencing revealed that gene A is frequently methylated in TSAs.

Research Products

• [Presentation] Subclasses of Type-II pit pattern reveal alternative tumorigenic pathways of colorectal serrated lesions (2016)
  • Author(s): Hironori Aoki, Eiichiro Yamamoto, Hiro-o Yamano, Tamotsu Sugai, Hiromu Suzuki
  • Organizer: 24th UEG Week
  • Place of Presentation: Austria Center Vienna, Austria
  • Year and Date: 2016-10-18
  • Int'l Joint Research
• [Presentation] Identification of aberrant DNA methylation associated with the development of colorectal traditional serrated adenoma and the possibility for CRC progression marker (2016)
  • Author(s): Hironori Aoki, Eiichiro Yamamoto, Hiro-o Yamano, Taku Harada, Tamotsu Sugai, Hiromu Suzuki
  • Organizer: ACG 2016 Annual Scientific Meeting & Postgraduate Course
  • Place of Presentation: Venetian Hotel and Resort - Las Vegas, USA
  • Year and Date: 2016-10-14
  • Int'l Joint Research
• [Presentation] 大腸鋸歯状腺腫の進展に関わるDNAメチル化異常の同定 (2016)
  • Author(s): 青木敬則, 山本英一郎, 山野泰穂, 萬顕, 石黒一也, 原田拓, 新沼猛, 甲斐正広, 足立靖, 遠藤高夫, 菅井有, 鈴木拓
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2016-10-06
• [Presentation] 大腸鋸歯状腺腫においてメチル化異常を示す遺伝子の同定とその検討 (2016)
  • Author(s): 青木敬則, 山本英一郎, 山野泰穂, 足立靖, 遠藤高夫, 菅井有, 鈴木拓
  • Organizer: 第27回日本消化器癌発生学会総会
  • Place of Presentation: 城山観光ホテル(鹿児島市)
  • Year and Date: 2016-09-15
• [Presentation] Identification of aberrant DNA methylation associated with the development of traditional serrated adenoma (2016)
  • Author(s): Hironori Aoki, Eiichiro Yamamoto, Hiro-o Yamano, Takeshi Niinuma, Masahiro Kai, Reo Maruyama, Yasushi Adachi, Takao Endo, Tamotsu Sugai and Hiromu Suzuki
  • Organizer: Tenth AACR-JCA Joint Conference on Breakthroughs in Cancer Research
  • Place of Presentation: Hyatt Regency Maui, USA
  • Year and Date: 2016-02-16
  • Int'l Joint Research
• [Presentation] 鋸歯状腺腫においてメチル化する遺伝子の同定と臨床病理・分子生物学的検討 (2015)
  • Author(s): 青木敬則, 山本英一郎, 山野泰穂, 新沼猛, 甲斐正広, 丸山玲緒, 足立靖, 遠藤高夫, 菅井有, 鈴木拓
  • Organizer: 第26回日本消化器癌発生学会総会
  • Place of Presentation: 米子全日空ホテル (米子市)
  • Year and Date: 2015-11-19
• [Presentation] Endoscopic and molecular features reveal progression of serrated lesions (2015)
  • Author(s): Hironori Aoki, Eiichiro Yamamoto, Hiro-o Yamano, Takao Endo, Tamotsu Sugai and Hiromu Suzuki
  • Organizer: 23rd UEG Week
  • Place of Presentation: Fira Barcelona, Spain
  • Year and Date: 2015-10-24
  • Int'l Joint Research
• [Presentation] 鋸歯状腺腫の発育進展に関わる新規遺伝子のメチル化同定のためのエピジェネティックスおよび臨床的特徴の統合解析 (2015)
  • Author(s): 青木敬則, 山本英一郎, 山野泰穂, 新沼猛, 甲斐正広, 丸山玲緒, 足立靖, 遠藤高夫, 菅井有, 鈴木拓
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場 (名古屋市)
  • Year and Date: 2015-10-08