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Development of Non-invasive Screening Tool to Detect Colorectal Neoplasia.

Research Project

Project/Area Number 20590572
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionOkayama University

Principal Investigator

NAGASAKA Takeshi  Okayama University, 病院, 助教 (30452569)

Co-Investigator(Kenkyū-buntansha) KONDOU Yoshitaka  岡山大学, 病院, 医員 (50534765)
TANAKA Noriaki  岡山大学, 大学院・医歯薬学総合研究科, 教授 (10127566)
KOBAYASHI Naoya  岡山大学, 病院, 講師 (10325102)
MATSUBARA Nagahide  岡山大学, 医学部・歯学部附属病院, 講師 (70314672)
SASAMOTO Hiromi  岡山大学, 大学院・医歯薬学総合研究科, 外国人客員研究員 (10452567)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords腫瘍検査学 / 大腸癌 / メチル化 / スクリーニング / 便潜血反応 / 検便 / 癌 / ゲノム / トランスレーショナルリサーチ / 遺伝子 / 臨床
Research Abstract

The development of noninvasive screening tests is important to reduce mortality from gastrointestinal neoplasia. We sought to develop such a test by analysis of DNA methylation from exfoliated cancer cells in feces. We developed a novel strategy that uses single-step modification of DNA with sodium bisulfite and fluorescence polymerase chain reaction methodology to measure aberrant methylation in fecal DNA. Methylation was analyzed in 296 fecal samples obtained from a variety of patients, including 21 with gastric tumors, 152 with colorectal tumors, and 10 with non-neoplastic or inflammatory lesions in the gastrointestinal lumen. The assay successfully identified one or more methylated markers in fecal DNA from 57.1% of patients with gastric cancer, 75.0% of patients with colorectal cancer, and 44.4% of patients with advanced colorectal adenomas, but only 10.6% of subjects without neoplastic or active diseases. Methylation in fecal DNA is associated with the presence of gastrointestinal tumors relative to non-neoplastic conditions. Our novel fecal DNA methylation assay provides a possible means to noninvasively screen not only for colorectal tumors but also for gastric tumors.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (34 results)

All 2010 2009 2008

All Journal Article (17 results) (of which Peer Reviewed: 16 results) Presentation (17 results)

  • [Journal Article] Somatic hypermethylation of MSH2 is a frequent event in Lynch Syndrome colorectalcancers.2010

    • Author(s)
      Nagasaka T, Rhees J, Kloor M, Gebert J, Naomoto Y, Boland CR, Goel A.
    • Journal Title

      Cancer Res. 70(8)

      Pages: 3098-3108

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] An optimized pentaplex PCR for detecting DNA mismatch repair-deficient colorectal cancers.2010

    • Author(s)
      Goel A, Nagasaka T, Hamelin R, Boland CR.
    • Journal Title

      PLoS One. 5(2)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic silencing of miR-137 is an early event in colorectal carcinogenesis.2010

    • Author(s)
      Balaguer F, Link A, Lozano JJ, Cuatrecasas M, Nagasaka T, Boland CR, Goel A.
    • Journal Title

      Cancer Res. 70(16)

      Pages: 6609-6618

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fecal MicroRNAs as novel biomarkers for colon cancer screening.2010

    • Author(s)
      Link A, Balaguer F, Shen Y, Nagasaka T, Lozano JJ, Boland CR, Goel A.
    • Journal Title

      Cancer Epidemiol Biomarkers Prev. 19(7)

      Pages: 1766-1774

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 便中メチル化DNA検出による消化器がんスクリーニング:消化器がんを非侵襲的にスクリーニングすることは可能か?2010

    • Author(s)
      永坂岳司, 田中紀章, 孫冬生, 猶本良夫, 松原長秀, 八木孝仁, 藤原俊義
    • Journal Title

      岡山医学会雑誌 第122巻

      Pages: 107-112

    • NAID

      130004505681

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 便中メチル化検出による消化器がんスクリーニング:消化器がんを非侵襲的にスクリーニングすることは可能か?2010

    • Author(s)
      永坂岳司
    • Journal Title

      岡山医学会雑誌

      Volume: 122 Pages: 107-112

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 遺伝子情報に基づいた大腸がん個別化治療へ KRAS/BRAF/MSI2010

    • Author(s)
      永坂岳司
    • Journal Title

      ファルマシア

      Volume: 1120 Pages: 1120-1124

    • NAID

      110009867669

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Epigenetic silencing of miR-137 is an early event in colorectal carcinogenesis.2010

    • Author(s)
      Francesc Balaguer
    • Journal Title

      Cancer Research

      Volume: 70 Pages: 6609-6618

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low frequency of Lynch syndrome among young patients with non-familial colorectal cancer.2010

    • Author(s)
      Ajay Goel
    • Journal Title

      Clinical gastroenterology and hepatology

      Volume: 8 Pages: 966-971

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fecal MicroRNAs as novel biomarkers for colon cancer screening2010

    • Author(s)
      Alexander Link
    • Journal Title

      Cancer Epidemiology, Biomarkers & Prevention

      Volume: 19 Pages: 1766-1764

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Somatic hypermethylation of MSH2 is a frequent event in Lynch Syndrome colorectal cancers.2010

    • Author(s)
      永坂岳司
    • Journal Title

      Cancer Research

      Volume: 128 Pages: 869-878

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An optimized pentaplex PCR for detecting DNA mismatch repair-deficient colorectal cancers.2010

    • Author(s)
      永坂岳司
    • Journal Title

      PLoS One

      Volume: 5

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of fecal DNA methylation to detect gastrointestinal neoplasia.2009

    • Author(s)
      Nagasaka T, Tanaka N, Cullings HM, Sun DS, Sasamoto H, Uchida T, Koi M, Nishida N, Naomoto Y, Boland CR, Matsubara N, Goel A.
    • Journal Title

      J Natl Cancer Inst. 101(18)

      Pages: 1244-1258

    • NAID

      130004505681

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of fecal DNA methylation to detect gastrointestinal neoplasia.2009

    • Author(s)
      Nagasaka T, Tanaka N, Cullings HM, Sun DS, Sasamoto H, Uchida T, et al.
    • Journal Title

      Journal of the National Cancer Institute 101(18)

      Pages: 1244-1258

    • NAID

      130004505681

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutations in both KRAS and BRAF may contribute to the methylator phenotype in colon cancer.2008

    • Author(s)
      Nagasaka T, Koi M, Kloor M, Gebert J, Vilkin A, Nishida N, Shin SK, Sasamoto H, Tanaka N, Matsubara N, Boland CR, Goel A.
    • Journal Title

      Gastroenterology. 134(7)

      Pages: 1950-1960

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Methylation pattern of the 06-methylguanine-DNA methyltransferase gene in colon during progressive colorectal tumorigenesis.2008

    • Author(s)
      Nagasaka T, Goel A, Notohara K, Takahata T, Sasamoto H, Uchida T, Nishida N, Tanaka N, Boland CR, Matsubara N
    • Journal Title

      Int J Cancer. 122(11)

      Pages: 2429-2436

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant methylation of multiple tumor suppressor genes in aging liver, chronic hepatitis, and hepatocellular carcinoma.2008

    • Author(s)
      Nishida N, Nagasaka T, Nishimura T, Ikai I, Boland CR, Goel A.
    • Journal Title

      Hepatology. 47(3)

      Pages: 908-918

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] An Optimized Pentaplex PCR for Detecting DNA Mismatch Repair-Deficient Colorectal Cancers2010

    • Author(s)
      永坂岳司
    • Organizer
      日本人類遺伝学会 第55回大会
    • Place of Presentation
      埼玉
    • Year and Date
      2010-10-27
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Somatic hypermethylation of MSH2 is a frequent event in lynch syndrome colorectal cancers(Lynch症候群大腸癌とMSH2メチル化)2010

    • Author(s)
      永坂岳司
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-23
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 大腸癌化学療法における個別化医療のためのKRAS/BRAF/MSIマトリックスの提案2010

    • Author(s)
      永坂岳司
    • Organizer
      第65回日本消化器外科学会総会
    • Place of Presentation
      山口
    • Year and Date
      2010-07-14
    • Related Report
      2010 Final Research Report
  • [Presentation] 大腸癌化学療法における個別化医療のためのKRAS/BRAF/MSIマトリックスの提案2010

    • Author(s)
      永坂岳司
    • Organizer
      第65回日本消化器外科学会総会
    • Place of Presentation
      下関
    • Year and Date
      2010-07-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] Imatinib耐性GISTに対するSunitinib使用経験2010

    • Author(s)
      藤原康宏
    • Organizer
      第65回日本消化器外科学会総会
    • Place of Presentation
      下関
    • Year and Date
      2010-07-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] 大腸癌肝転移における集学的治療戦略~肝切除術前・術後化学療法の効果~2010

    • Author(s)
      楳田祐三
    • Organizer
      第65回日本消化器外科学会総会
    • Place of Presentation
      下関
    • Year and Date
      2010-07-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] KRAS/BRAF/MSI分類による術前からの大腸癌治療戦略構築の提案2010

    • Author(s)
      永坂岳司
    • Organizer
      第73回大腸癌研究会
    • Place of Presentation
      奄美
    • Year and Date
      2010-07-02
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 大腸癌バイオマーカーの未来2010

    • Author(s)
      永坂岳司
    • Organizer
      Chugai Colorectal Cancer Conference
    • Place of Presentation
      大阪
    • Year and Date
      2010-05-20
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 大腸癌化学療法における当院での問題点2010

    • Author(s)
      藤原康宏
    • Organizer
      第110回日本外科学会定期学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2010-04-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Analysis of fecal DNA methylation for detecting gastrointestinal neoplasia2009

    • Author(s)
      永坂岳司
    • Organizer
      第64回日本消化器外科学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2009-07-16
    • Related Report
      2010 Final Research Report
  • [Presentation] Differental mutation of BRAF/KRAS in primary and liver metastatis of colon cancer2009

    • Author(s)
      谷口信将
    • Organizer
      第64回日本消化器外科学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2009-07-16
    • Related Report
      2010 Final Research Report
  • [Presentation] Genetic and epigenetic alterations of netrin receptors in gastric cancer2009

    • Author(s)
      岡哲弘
    • Organizer
      第64回日本消化器外科学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2009-07-16
    • Related Report
      2010 Final Research Report
  • [Presentation] 初発大腸癌と肝転移巣におけるKRAS/BRAF突然変異の検出および解析~必要な感度は?一致率は?2009

    • Author(s)
      永坂岳司
    • Organizer
      第91回日本消化器病学会中国支部例会
    • Place of Presentation
      岡山
    • Year and Date
      2009-06-13
    • Related Report
      2010 Final Research Report
  • [Presentation] Gene Expression Profiling Identifies Loss of Fhit Expression Due to Epigenetic Silencing As a Frequent Event in African American (AA) Patients with Colorectal Cancer (CRC)2009

    • Author(s)
      Ajay Goel
    • Organizer
      Digestive Disease Week 2009
    • Place of Presentation
      Chicago
    • Related Report
      2010 Final Research Report
  • [Presentation] Genetic and Epigenetic Alterations of Netrin Receptors in Gastric Cancer2009

    • Author(s)
      Keisuke Toda
    • Organizer
      Digestive Disease Week 2009
    • Place of Presentation
      Chicago
    • Related Report
      2010 Final Research Report
  • [Presentation] Analysis of fecal DNA methyloation for detecting gastrointestinal neoplasia2008

    • Author(s)
      永坂岳司
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-29
    • Related Report
      2010 Final Research Report
  • [Presentation] Analysis of fecal DNA methyloation for detecting gastrointestinal neoplasia2008

    • Author(s)
      永坂 岳司
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2008-10-29
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-11-11  

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