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Studies on genomic instability of gastric cancer

Research Project

Project/Area Number 10671162
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionTokyo Medical and Dental University

Principal Investigator

NIHEI Zenro  Tokyo Medical & Dental University, associate professor, 大学院・医歯学総合研究科, 助教授 (00189341)

Co-Investigator(Kenkyū-buntansha) OSANAI Takayuki  Tokyo Medical & Dental University, instructor, 大学院・医歯学総合研究科, 助手 (50301164)
ICHIKAWA Wataru  Tokyo Medical & Dental University, instructor, 大学院・医歯学総合研究科, 助手 (70282738)
飯田 聡  東京医科歯科大学, 医学部, 助手
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsGastric cancer / E-cadherin / p14^<ARF> gene / methylation / genomic instability / MSI / 家族性胃癌 / E-cadherin
Research Abstract

Despite a decreasing incidence, gastric cancer remains a major cause of cancer death worldwide. Recently, in three FGC kindreds in New Zealand, germ-line mutations of the E-cadherin gene were found. To determine whether or not nerm-line mutation of the E-cadherin gene is also responsible for the predisposition to Japanese FGC, we analyzed all of the exons of E-cadherin by PCR-single-strand conformational polymorphism analysis in 16 patients from 14 Japanese familial gastric cancer(FGC)kindreds. However, no germ-line mutation was detected, suggesting that a predisposition to FGCs by E-dacherin gene mutation is infrequent in Japanese cases.
p 14^<ARF>, generated through an alternative splicing process that replaces the first exon, Ia, of p16^<1NK4a> with exon Ib, located > 15kb upstream of exon Ia, has been shown to function as a growth suppressor. We examined 11 gastric cancer cell lines for mRNA expression, homozygous deletion, mutation, and promoter methylation of the p 14^<ARF> gene. No mRNA expression was detected in 5 of the 7 diffuse-type cell lines. All intestinal cell lines displayed normal levels of expression except for one with a low level of expression. Of the 3 cell lines without expression, 3(MKN45, NUGC-2, and NUGC-4)and 1(KATO III)displayed homozygous deletion and methylation of the p 14^<ARF> gene, respectively. No mutation was found in the whole coding region of the p 14^<ARF> gene in 8 cell lines without homozygous deletion. Our results indicate that the p 14^<ARF> gene is more frequently inactivated by homozygous deletion or methylation in diffuse-type gastric cancer cell lines(5/7, 71.4%)than in intestinal ones(0/4, P=0.022). When we also analyzed 62 primary gastric cancers for the methylation status of the p 14^<ARF> promoter region, the methylation frequency tended to be higher in diffuse-type gastric cancers(15/33, 45.5%)than in intestinal ones(7/28, 25%). Thus, p 14^<ARF> alterations might be involved in diffuse-type gastric carcinogenesis.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] S. Iida, W. Ichikawa, Z. Nihei et al: "Infrequent gern-line mutation of the E-calherin gene in Japanese familial gastric cauca kindrods"Clinical Cancer Research. 5. 1445-1447 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S. Iida, W. Ichikawa, Z. Nihei: "Alterations and hypermethylation of the p14^<ARF> gene in gastric concer"Int. J. Cancer. 87. 654-658 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 仁瓶善郎、飯田聡、杉原健一: "家族性胃癌"日本臨床. 58. 1523-1526 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Iida, W.Ichikawa, Z.Nihei, et al.: "Infrequent germ-line mutation of the E-cadherin gene in Japanese familial gastric cancer kindreds"Clinical Cancer Research. 5. 1445-1447 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Iida, W.Ichikawa, Z.Nihei et al.: "Alterations and hypermethylation of the p14^<ARF> gene in gastric cancer"Int.J.Cancer. 87. 654-658 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Z.Nihei, S.Iida, K.Sugihara: Nihon Rinshyo. 58. 1523-1526 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Iida,W.Ichikawa,E.Nihei et al: "Infrequent germ-line mutation of the E-cadherin gene in Japanese familial gastric cancer kindreds"Clinical Cancer Research. 5. 1445-1447 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Iida,W,Ichikawa,E.Nihei et al: "Alterations and hyermethylation of the p14ARF gene in gastric cancer"Int.J.Cancer. 87. 654-658 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 仁瓶善郎,飯田聡,杉原健一: "家族性胃癌"日本臨床. 58・7. 1523-1526 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Iida S, Akiyama Y, Ichikawa W, et al,: "Infrequent germ-Line mutation of the E-cadherin gene in Japanese familial gastric cancer kindreds"Clinical Cancer Research. 5. 1445-1447 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 飯田 聡 他: "家族性胃癌における臨床病理学的検討とE-カドヘリン遺伝子変異の検索" 消化器癌の発生と進展. 10. 405-408 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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