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Demethylation alteration induced by H. Pylori infection and its relation to chromosomal instability

Research Project

Project/Area Number 16K10515
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionJichi Medical University

Principal Investigator

SAITO Masaaki  自治医科大学, 医学部, 講師 (00382911)

Co-Investigator(Kenkyū-buntansha) 鈴木 浩一  自治医科大学, 医学部, 准教授 (70332369)
力山 敏樹  自治医科大学, 医学部, 教授 (80343060)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsセントロメア / 脱メチル化異常 / 染色体不安定性 / Satellite RNA / 脱メチル化 / 胃癌 / Satelliteα transcript / CENPA蛋白 / H.pylori感染 / Satelliteα配列
Outline of Final Research Achievements

We previously reported that overexpression of satellite alpha transcript (SAT) facilitates chromosomal instability, which is involved in the development of multiple tumors in patients with colorectal. The centromere consists of satellite alpha repetitive sequences, which are ideal targets for DNA hypomethylation, resulting in the overexpression of SAT. In this study, we elucidated the significance of DNA demethylation of SAT in the development of multiple tumors in patients with gastric cancer. Relative demethylation level of SAT was calculated from 103 gastric patients. Patients with multiple gastric cancer (n=20) showed higher demethylation levels than those in patients with single cancer (n=83, P<0.001). Additionally, multivariate analysis revealed that the demethylation level of SAT was a significant factor for predicting multiple gastric cancer (P=0.008). Our data indicated that DNA demethylation of SAT was involved in the development of multiple gastric cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究によってセントロメア領域の脱メチル化異常による発癌の機序として、Satellite transcriptの転写が亢進し、RNAi機構やセントロメア蛋白の発現が助長され、染色体不安定性が誘導される事が考えられた。この経路にはp53蛋白の変異は関与しておらず、古典的な分化型胃癌の発癌過程とは異なるSatelliteαの脱メチル化を介する新たな発癌経路の発見の糸口となる事が期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (34 results)

All 2018 2017 2016

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 7 results) Presentation (23 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results)

  • [Journal Article] Monitoring circulating tumor DNA revealed dynamic changes in KRAS status in patients with metastatic colorectal2018

    • Author(s)
      Yuji Takayama, Koichi Suzuki, Yuta Muto, Kosuke Ichida, Taro Fukui, Nao Kakizawa, Hideki Ishikawa, Fumiaki Watanabe, Fumi Hasegawa, Masaaki Saito, Shingo Tsujinaka, Kazushige Futsuhara, Yasuyuki Miyakura, Hiroshi Noda, Fumio Konishi, Toshiki Rikiyama
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 36 Pages: 24398-24413

    • DOI

      10.18632/oncotarget.25309

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Methylation-Sensitive Amplification Length Polymorphism (MS-AFLP) Microarrays for Epigenetic Analysis of Human Genomes2018

    • Author(s)
      Alonso Sergio、Suzuki Koichi、Yamamoto Fumiichiro、Perucho Manuel
    • Journal Title

      Methods in molecular biology

      Volume: 1766 Pages: 137-156

    • DOI

      10.1007/978-1-4939-7768-0_8

    • ISBN
      9781493977673, 9781493977680
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Overexpression of satellite alpha transcripts leads to chromosomal instability via segregation errors at specific chromosomes.2018

    • Author(s)
      Ichida K, Suzuki K, Fukui T, Takayama Y, Kakizawa N, Watanabe F, Ishikawa H, Muto Y, Kato T, Saito M, Futsuhara K, Miyakura Y, Noda H, Ohmori T, Konishi F, Rikiyama T.
    • Journal Title

      Int J Oncol.

      Volume: - Pages: 1685-1693

    • DOI

      10.3892/ijo.2018.4321

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A High Abdominal Aortic Calcification Score on CT is a Risk Factor for Postoperative Pancreatic Fistula in Elderly Patients Undergoing Pancreaticoduodenectomy2017

    • Author(s)
      Kakizawa Nao、Noda Hiroshi、Watanabe Fumiaki、Ichida Kosuke、Suzuki Koichi、Rikiyama Toshiki
    • Journal Title

      World Journal of Surgery

      Volume: 42 Issue: 4 Pages: 1129-1137

    • DOI

      10.1007/s00268-017-4240-z

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] En bloc pancreaticoduodenectomy and right hemicolectomy for locally advanced right-sided colon cancer2017

    • Author(s)
      Kaneda Yuji、Noda Hiroshi、Endo Yuhei、Kakizawa Nao、Ichida Kosuke、Watanabe Fumiaki、Kato Takaharu、Miyakura Yasuyuki、Suzuki Koichi、Rikiyama Toshiki
    • Journal Title

      World Journal of Gastrointestinal Oncology

      Volume: 9 Issue: 9 Pages: 372-372

    • DOI

      10.4251/wjgo.v9.i9.372

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significance of the Difference in the Size of Liver Tumors in the Management of Patients with Colorectal Liver Metastases2017

    • Author(s)
      Ichida Kosuke、Suzuki Koichi、Fukui Taro、Takayama Yuji、Kakizawa Nao、Muto Yuta、Kato Takaharu、Hasegawa Fumi、Watanabe Fumiaki、Kaneda Yuji、Kikugawa Rina、Saito Masaaki、Tsujinaka Shingo、Futsuhara Kazushige、Miyakura Yasuyuki、Noda Hiroshi、Kiyozaki Hirokazu、Rikiyama Toshiki
    • Journal Title

      Journal of Molecular and Genetic Medicine

      Volume: 11 Issue: 1

    • DOI

      10.4172/1747-0862.1000254

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Morphological response contributes to patient selection for rescue liver resection in chemotherapy patients with initially un-resectable colorectal liver metastasis2017

    • Author(s)
      Suzuki Koichi、Muto Yuta、Ichida Kosuke、Fukui Taro、Takayama Yuji、Kakizawa Nao、Kato Takaharu、Hasegawa Fumi、Watanabe Fumiaki、Kaneda Yuji、Kikukawa Rina、Saito Masaaki、Tsujinaka Shingo、Futsuhara Kazushige、Takata Osamu、Noda Hiroshi、Miyakura Yasuyuki、Kiyozaki Hirokazu、Konishi Fumio、Rikiyama Toshiki
    • Journal Title

      Oncology Letters

      Volume: 14 Issue: 2 Pages: 1491-1499

    • DOI

      10.3892/ol.2017.6338

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Herpes simplex virus-1 encephalitis induced by chemoradiotherapy and steroids in an esophageal cancer patient2016

    • Author(s)
      Saito M
    • Journal Title

      BMC Cancer

      Volume: 16 Pages: 233-233

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Two Cases with Perforation of the Large Intestine after Upper Gastrointestinal Series with Barium2016

    • Author(s)
      Saito M
    • Journal Title

      Journal of Surgery

      Volume: 5 Issue: 4 Pages: 5-5

    • DOI

      10.16966/2470-0991.131

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Heterogeneous expression of zinc-finger E-box-binding homeobox 1 plays a pivotal role in metastasis via regulation of miR-200c in epithelial-mesenchymal transition2016

    • Author(s)
      Muto Y
    • Journal Title

      International Journal of Oncology

      Volume: 49 Pages: 1057-1067

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Malignant, but not benign, intraductal papillary mucinous neoplasm preferentially associates with prior extrapancreatic malignancies2016

    • Author(s)
      Kato T
    • Journal Title

      Oncology Reports

      Volume: 35 Pages: 3236-3240

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] Clinical significance of monitoring KRSA in tissue and serum of pancreatic cancer patients2018

    • Author(s)
      Watanabe F, Suzuki K, Ishikawa H, Endo Y, Ichida K, Takayama Y, Fukui T, Kakizawa N, Kasahara N, Kato T, Noda H, Rikiyama T
    • Organizer
      Gastrointestinal Cancers Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dynamics and characteristics of KRAS mutated circulating tumor DNA in patients with metastatic colorectal cancer during various treatments2018

    • Author(s)
      Takayama Y, Suzuki K, Ichida K, Fukui T, Kakizawa N, Watanabe F, Kikukawa R, Hasegawa F, Tsujinaka S, Miyakura Y, Konishi F, Rikiyama T
    • Organizer
      Gastrointestinal Cancers Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Liquid biopsy leads to a paradigm shift in colorectal cancer treatments2018

    • Author(s)
      Suzuki K, Takayama Y, Kakizawa N, Ichida K, Fukui T, Watanabe F, Ishikawa H, Saito M, Miyakura Y, Rikiyama T
    • Organizer
      第73回日本消化器外科学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] リキッドバイオプシーによる大腸癌診療のパラダイムシフト2018

    • Author(s)
      鈴木浩一
    • Organizer
      Saitama CRC Seminar
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 膵癌に対する組織と血中のKRASモニタリングの有用性2018

    • Author(s)
      渡部文昭、鈴木浩一、遠藤裕平、笠原尚哉、加藤高晴、齊藤正昭、辻仲眞康、宮倉安幸、野田弘志、清崎浩一、力山敏樹
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 膵癌に対する術前治療に組織と血中のKRASモニタリングは有用か2018

    • Author(s)
      渡部文昭、鈴木浩一、力山敏樹
    • Organizer
      第104回日本消化器病学会総会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Clinical significance of monitoring KRAS in tissue and plasma of pancreatic cancer patients2018

    • Author(s)
      Watanabe F
    • Organizer
      第17回自治医科大学シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Significance of monitoring vascular endothelial growth factor signals in blood during treatment of colorectal cancer patients2018

    • Author(s)
      Kakizawa N, Suzuki K, Ishikawa H, Watanabe F, Kikugawa R, Tsujinaka S, Miyakura Y, Rikiyama T
    • Organizer
      第17回自治医科大学シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Significance of monitoring VEGF signals in blood during treatment of colorectal cancer patient2018

    • Author(s)
      柿澤奈緒、鈴木浩一、石川英樹、渡部文昭、辻仲眞康、宮倉安幸、力山敏樹
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] リキッドバイオプシーによるがん診療のパラダイムシフト2018

    • Author(s)
      鈴木浩一
    • Organizer
      第27回日本がん転移学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] DNA脱メチル化異常をバイオマーカーとする胃切除範囲への臨床応用2018

    • Author(s)
      齊藤正昭、清崎浩一、小櫃 保、伊瀬谷和輝、石岡大輔、辻仲眞康、宮倉安幸、鈴木浩一、野田弘志、力山敏樹
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The clinical significance of KRAS monitoring in tumor tissues and blood of patients with pancreatic tumor2017

    • Author(s)
      Watanabe F, Suzuki K, Ichida K, Takayama Y, Fukui T, Kakizawa N, Rikiyama T
    • Organizer
      Gastrointestinal Cancers Symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Appearance of KRAS mutated circulating tumor DNA during various treatments for metastatic colorectal cancer patients2017

    • Author(s)
      Takayama Y, Suzuki K, Ichida K, Fukui T, Kakizawa N, Watanabe F, Hasegawa F, Tsujinaka S, Miyakura Y, Noda H, Rikiyama T
    • Organizer
      Exosomes and Liquid Biopsies ASIA
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Liquid Biopsyによるがん診療のパラダイムシフト2017

    • Author(s)
      鈴木浩一、高山裕司、渡部文昭、市田晃佑、福井太郎、柿澤奈緒、齊藤正昭、辻仲眞康、蓬原一茂、宮倉安幸、力山敏樹
    • Organizer
      第26回日本癌病態治療研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] セントロメア領域の脱メチル化は、染色体不安定性を誘導する2017

    • Author(s)
      齊藤正昭、鈴木浩一、市田晃佑、高橋洵、石岡大輔、小櫃保、清崎浩一、力山敏樹
    • Organizer
      第89回日本胃癌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 乳癌両側発生、多臓重複器発生に関わる染色体分配の異常とSatellite alpha transcripts2017

    • Author(s)
      蓬原一茂、柿澤奈緒、鈴木浩一、齊藤正昭、市田晃佑、佐藤あい、吉沢あゆは、野口友里、尾本きよか、力山敏樹
    • Organizer
      第25回乳癌学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 膵腫瘍性病変における組織と血中のKrasモニタリングの臨床的意義2017

    • Author(s)
      渡部文昭、鈴木浩一、遠藤裕平、市田晃佑、福井太郎、柿澤奈緒、兼田裕司、野田弘志、力山敏樹
    • Organizer
      第117回日本外科学会定期学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 乳癌においてSatellite alpha transcript過剰発現が惹起する染色体不安定性2017

    • Author(s)
      市田晃佑、鈴木浩一、福井太郎、高山裕司、柿澤奈緒、渡部文昭、石川英樹、齊藤正昭、武藤雄太、加藤高晴、蓬原一茂、力山敏樹
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Specific chromosomes were impaired by overexpression of Satellite alpha transcript in breast cancer patients2017

    • Author(s)
      市田晃佑、鈴木浩一、高山裕司、福井太郎、渡部文昭、柿澤奈緒、石川英樹、加藤高晴、齊藤正昭、力山敏樹
    • Organizer
      第16回自治医科大学シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] 治療中の転移性大腸癌患者におけるKRAS変異型血中遊離DNA出現パターンの同定2017

    • Author(s)
      高山裕司、鈴木浩一、市田晃佑、福井太郎、渡部文昭、菊川利奈、長谷川芙美、辻仲眞康、宮倉安幸、野田弘志、小西文雄、力山敏樹
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Appearance and characteristic of KRAS mutated circulating tumor DNA in patients with metastatic colorectal cancer during various treatments2017

    • Author(s)
      高山裕司
    • Organizer
      第16回自治医科大学シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] Aberrant DNA demethylation is a biomarker of cancer susceptibility2016

    • Author(s)
      齊藤 正昭
    • Organizer
      日本消化器癌発生学会
    • Place of Presentation
      鹿児島
    • Year and Date
      2016-10-15
    • Related Report
      2016 Research-status Report
  • [Presentation] Satellite alpha transcript過剰発現が引き起こす染色体不安定性2016

    • Author(s)
      市田 晃佑
    • Organizer
      日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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