Identification of genetic factors involved in the development of familial gastric cancer in Japanese population

• Project/Area Number: 21790383
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: YAMADA Hidetaka 浜松医科大学, 医学部, 特任研究員 (30397400)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 家族性胃がん / 生殖細胞系列変異 / コピー数異常 / E-カドヘリン / CDH1 / MLPA法 / DNAメチル化 / 網羅的遺伝子発現解析 / 変異 / 胃がん / 若年胃がん

Research Abstract

Germline mutation and copy number alteration of the CDH1 gene were identified in familial gastric cancer in Japanese population. Functional analysis showed that these mutations contribute to carcinogenesis in patients with familial gastric cancer. Germline mono-allelic hypermethylation of the CDH1 promoter is not a major predisposing factor for gastric cancer. Global gene expression analysis showed that level of expression of several gene have varied in the familial gastric cancer group.

Research Products

• [Journal Article] A novel tumor-derived SGOL1 variant causes abnormal mitosis and unstable chromatid cohesion (2011)
  • Author(s): Kahyo T, Iwaizumi M, Shinmura K, Matsuura S, Nakamura T, Watanabe Y, Yamada H, Sugimura H
  • Journal Title: Oncogene Volume: 30 Pages: 4453-63
  • Peer Reviewed
• [Journal Article] Reduced expression of MUTYH with suppressive activity against mutations caused by 8-hydroxyguanine is a novel predictor of a poor prognosis in human gastric cancer (2011)
  • Author(s): Shinmura K, Goto M, Suzuki M, Tao H, Yamada H, Igarashi H, Matsuura S, Maeda M, Konno H, Matsuda T, Sugimura H
  • Journal Title: J Pathol Volume: 225 Pages: 414-23
  • Peer Reviewed
• [Journal Article] Germline alterations in the CDH1 gene in familial gastric cancer in the Japanese population (2011)
  • Author(s): Yamada H, Shinmura K, Ito H, Kasami M, Sasaki N, Shima H, Ikeda M, Tao H, Goto M, Ozawa T, Tsuneyoshi T, Tanioka F, Sugimura H
  • Journal Title: Cancer Sci Volume: 102 Pages: 1782-8
  • NAID: 10030243664
  • Peer Reviewed
• [Journal Article] Aberrant expression and mutation-inducing activity of AID in human lung cancer (2011)
  • Author(s): Shinmura K, Igarashi H, Goto M, Tao H, Yamada H, Matsuura S, Tajima M, Matsuda T, Yamane A, Funai K, Tanahashi M, Niwa H, Ogawa H, Sugimura H
  • Journal Title: Ann Surg Oncol Volume: 18 Pages: 2084-92
  • Peer Reviewed
• [Journal Article] Germline alterations of the CDH1 gene in familial gastric cancer in the Japanese population (2011)
  • Author(s): Yamada H, et.al
  • Journal Title: Cancer Science Volume: 102 Issue: 10 Pages: 1782-1788
  • DOI: 10.1111/j.1349-7006.2011.02038.x
  • NAID: 10030243664
  • Peer Reviewed
• [Journal Article] Reduced expression of MUTYH with suppressive activity against mutations caused by 8-hydroxyguanine is a novel predictor of a poor prognosis in human gastric cancer (2011)
  • Author(s): Shinmura, et.Al
  • Journal Title: The Journal of Pathology Volume: 225 Issue: 3 Pages: 414-423
  • DOI: 10.1002/path.2953
  • Peer Reviewed
• [Journal Article] Identification of 5 novel germline APC mutations and characterization of clinical phenotypes in Japanese patients with classical and attenuated familial adenomatous polyposis (2010)
  • Author(s): Tao H, Shinmura K, Yamada H, Maekawa M, Osawa S, Takayanagi Y, Okamoto K, Terai T, Mori H, Nakamura T, Sugimura H
  • Journal Title: BMC Res Notes Volume: 3 Pages: 305-305
  • NAID: 120005305356
  • Peer Reviewed
• [Journal Article] Adenine DNA glycosylase activity of 14 Human MutY homolog(MUTYH) variant proteins found in patients with colorectal polyposis and cancer (2010)
  • Author(s): Goto M, Shinmura K, Nakabeppu Y, Tao H, Yamada H, Tsuneyoshi T, Sugimura H
  • Journal Title: Hum Mutat Volume: 31
  • Peer Reviewed
• [Journal Article] Association between neuropeptide Y receptor 2 polymorphism and the smoking behavior of elderly Japanese (2010)
  • Author(s): Sato N, Kageyama S, Chen R, Suzuki M, Mori H, Tanioka F, Yamada H, Kamo T, Tao H, Shinmura K, Nozawa A, Sugimura H
  • Journal Title: J Hum Genet Volume: 55 Pages: 755-60
  • NAID: 10030737683
  • Peer Reviewed
• [Journal Article] Identification and characterization of a novel germline p53 mutation in a patient with glioblastoma and colon cancer (2009)
  • Author(s): Yamada H, Shinmura K, Yamamura Y, Kurachi K, Nakamura T, Tsuneyoshi T, Yokota N, Maekawa M, Sugimura H
  • Journal Title: Int J Cancer Volume: 125 Pages: 973-6
  • Peer Reviewed
• [Journal Article] Absence of germline mono-allelic promoter hypermethylation of the CDH1 gene in gastric cancer patients (2009)
  • Author(s): Yamada H, Shinmura K, Goto M, Iwaizumi M, Konno H, Kataoka H, Yamada M, Ozawa T, Tsuneyoshi T, Tanioka F, Sugimura H
  • Journal Title: Mol Cancer Volume: 8 Pages: 63-63
  • NAID: 120005314218
  • Peer Reviewed
• [Journal Article] Altered expression of the human base excision repair gene NTH1 in gastric cancer (2009)
  • Author(s): Goto M, Shinmura K, Igarashi H, Kobayashi M, Konno H, Yamada H, Iwaizumi M, Kageyama S, Tsuneyoshi T, Tsugane S, Sugimura H
  • Journal Title: Carcinogenesis Volume: 30 Pages: 1345-52
  • Peer Reviewed
• [Journal Article] Human Sgo1 Down-regulation Leads to Chromosomal Instability in Colorectal Cancer (2009)
  • Author(s): Iwaizumi M, Shinmura K, Mori H, Yamada H, Suzuki M, Kitayama Y, Igarashi H, Nakamura T, Suzuki H, Watanabe Y, Hishida A, Ikuma M, Sugimura H
  • Journal Title: Gut Volume: 58 Pages: 249-60
  • Peer Reviewed
• [Journal Article] Absence of germline mono-allelic promoter hypermethylation of the CDH1 gene in gastric cancer patients. (2009)
  • Author(s): Yamada H, et.al.
  • Journal Title: Molecular Cancer 8
  • NAID: 120005314218
  • Peer Reviewed
• [Presentation] Absence of germline mono-allelic promoter hypermethylation of the CDH1 gene in gastric cancer patients. (2010)
  • Author(s): 山田英孝
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-09-23
• [Presentation] Absence of germline mono-allelic promoter hypermethylation of the CDH1 gene in gastric cancer patients (2010)
  • Author(s): Yamada Hidetaka, Shinmura Kazuya, Mori Hiroki, Goto Masanori, Iwaizumi Moriya, Konno Hiroyuki, Kataoka Hideki, Yamada Masami, Ozawa Takachika
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] Identification and characterization of a novel germline p53 mutation in a patient with glioblastoma and colon cancer (2009)
  • Author(s): Yamada Hidetaka, Shinmura Kazuya, Yamamura Yasuhiro, Kurachi Kiyotaka, Nakamura Toshio, Tsuneyoshi Toshihiro, Yokota Naoki, Maekawa Masato, Sugimura Haruhiko
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 神経膠芽腫と大腸がんを発症した患者におけるp53遺伝子の新規生殖細胞系列変異の同定および機能解析 (2009)
  • Author(s): 山田英孝、新村和也、山村泰弘、倉地清隆、中村利夫、常吉俊宏、横田尚樹、前川真人、椙村春彦
  • Organizer: がん予防大会2009愛知
  • Place of Presentation: 名古屋