2001 Fiscal Year Annual Research Report

胃がん発症に関与する遺伝子の解明

Research Project

Project/Area Number	12212002
Research Institution	Research Institute, International Medical Center of Japan
Principal Investigator	笹月健彦国立国際医療センター, 研究所, 所長 (50014121)
Co-Investigator(Kenkyū-buntansha)	松野正紀東北大学, 医学部, 教授 (80004737) 佐々木泰史札幌医科大学, 医学部, 助手 (70322328) 有村佳昭札幌医科大学, 医学部, 助手 (80305218) 源利成金沢大学, がん研究所, 助教授 (50239323) 三輪晃一金沢大学, 医学部, 教授 (80019968)
Keywords	全ゲノムスキャン / 胃がん / 連鎖解析 / 相関解析 / マイクロサテライトマーカー / SNPs / ゲノム / 多因子疾患
Research Abstract	細胞のがん化は、複数の遺伝要因と複数の環境要因とが多段階で相互作用を繰り返すことで引き起こされる。遺伝性がんあるいはがん多発家系を解析することにより、網膜芽細胞腫の原因遺伝子であるRb遺伝子、ウィルムス腫瘍のWT-1遺伝子あるいは家族性乳癌の原因遺伝子であるBRCA-1、BRCA-2、などが同定され、がんの多発家系は、発がんの遺伝要因を解明する上で貴重な研究対象となる。本研究においては、胃がん発症を規定する遺伝要因を同定するために、1)胃がん発症同胞対を対象として、400個のマイクロサテライトマーカーを用い罹患同胞対法による全ゲノムスキャンを行うこと、2)1)によって同定された連鎖領域について、新たなマイクロサテライトマーカーあるいはgSNPsを設定し、胃がん発症例と日本人健常対照群間で相関検定を行うこと、により胃がん発症の責任遺伝子を同定することを目的としている。本年度は、これまでに収集された118組の胃がん発症同胞対を対象とした全ゲノムスキャンを行い、1)1番染色体1p32、D1S2890近傍、2番染色体2q33-34、D2S325近傍、11番染色体11p12-13、D11S935近傍に多点解析でLOD値がそれぞれ1.3、1.5、1.5を示す領域を同定した。2)21番染色体21q11、D21S1256に多点解析でLOD値が2.0を示す領域を同定した。これらの領域をさらに狭めるための相関解析の対象となる胃がん孤発症例の検体収集を行い、これまでに400症例からDNAが抽出・保存された。また、21番染色体候補領域においては相関解析のためのマイクロサテライトマーカーをゲノム配列をもとに170個同定した。21番染色体については、これらのマーカーを用いた相関検定による候補領域の絞込みを実施するとともに、他の領域についても、同様の手法による物理マッピングを行う予定である。

Research Products
(17 results)

All Other

All Publications (17 results)

[Publications] Oono T: "Organ-specific autoimmunity in mice whose T cell repertoire is shaped by a single antigenic peptide"J. Clin. Invest.. 108. 1589-1596 (2001)
[Publications] Fukui Y: "Hematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration"Nature. 412. 826-831 (2001)
[Publications] Sakai K: "Identification of susceptibility loci for autoimmune thyroid disease to 5q31-q33 and Hashimoto's thyroiditis to 8q23-q24 by multipoint affected sib-pair linkage analysis in Japan"Hum. Mol. Genet.. 10. 1379-1386 (2001)
[Publications] Kitagawa Y: "Laparoscopic detection of sentinel lymph nodes in gastrointestinal cancer.A novel and minimally invasive approach"Ann. Surg. Oncol.. 8(9S). 86-89 (2001)
[Publications] Ishigami S: "Invariant chain expression in gastric cancer"Cancer Letters. 168. 87-89 (2001)
[Publications] Kaneko K: "Detection of peritoneal micrometastases of gastric carcinoma with green fluorescen protein and carcinoembryonic antigen promoter"Cancer Res. 61. 5570-5574 (2001)
[Publications] Seto Y: "Lymph node metastasis and preoperative diagnosis of depth of invasion in early gastric cancer"Gastric Cancer. 4. 34-38 (2001)
[Publications] Minamoto T: "Distinct pattem of p53 phosphorylation in human tumors"Oncogene. 20. 3341-3347 (2001)
[Publications] Kanamori M: "Segregation analysis of gastric cancer in a Japanese population"Int J Human Genet. 1. 263-270 (2001)
[Publications] Sasaki Y: "Adenovirus-mediated transfer of the p53 family genes, p73 and p51/p63 induces cell cycle arrest and apoptosis in colorectal cancer cell lines : Potential application to gene therapy of colorectal cancer"Gene Therapy. 8. 1401-1408 (2001)
[Publications] Baba I: "Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-ras signaling pathway in human colon cancer cells"Cancer Res.. 60. 6886-6889 (2000)
[Publications] Ries S.: "Opposing effects of Ras on p53 : Transcriptional Activation of mdm2 and inductior of p19ARF"Cell. 103. 321-330 (2000)
[Publications] Shuang-Yin H.: "Functional evaluation of PTEN missense mutations using in vitro phosphoinositide phosphatase assay"Cancer Res. 60. 3147-3151 (2000)
[Publications] Keicho N: "Fine localization of a major disease-susceptibility locus for diffuse panbronchiolitis"Am J Hum Genet. 66. 501-507 (2000)
[Publications] Katai H: "Evaluation of the New International Union Against Cancer TNM staging for gastri carcinoma"Cancer. 88. 1796-1800 (2000)
[Publications] Nakamura K: "Morphometric analysis of regional lymph nodes with and without metastasis from early gastric cancinoma"Cancer. 88. 2438-2442 (2000)
[Publications] Ott I: "Reversible regulation of tissue factor-induced coagulation by glycosyl phosphatidylinositol-anchored tissue factor pathway inhibitor"Thromb Vasc Biol.. 20. 874-882 (2000)

2001 Fiscal Year Annual Research Report

胃がん発症に関与する遺伝子の解明

Principal Investigator

笹月 健彦 国立国際医療センター, 研究所, 所長 (50014121)

Research Products

[Publications] Oono T: "Organ-specific autoimmunity in mice whose T cell repertoire is shaped by a single antigenic peptide"J. Clin. Invest.. 108. 1589-1596 (2001)

[Publications] Fukui Y: "Hematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration"Nature. 412. 826-831 (2001)

[Publications] Sakai K: "Identification of susceptibility loci for autoimmune thyroid disease to 5q31-q33 and Hashimoto's thyroiditis to 8q23-q24 by multipoint affected sib-pair linkage analysis in Japan"Hum. Mol. Genet.. 10. 1379-1386 (2001)

[Publications] Kitagawa Y: "Laparoscopic detection of sentinel lymph nodes in gastrointestinal cancer.A novel and minimally invasive approach"Ann. Surg. Oncol.. 8(9S). 86-89 (2001)

[Publications] Ishigami S: "Invariant chain expression in gastric cancer"Cancer Letters. 168. 87-89 (2001)

[Publications] Kaneko K: "Detection of peritoneal micrometastases of gastric carcinoma with green fluorescen protein and carcinoembryonic antigen promoter"Cancer Res. 61. 5570-5574 (2001)

[Publications] Seto Y: "Lymph node metastasis and preoperative diagnosis of depth of invasion in early gastric cancer"Gastric Cancer. 4. 34-38 (2001)

[Publications] Minamoto T: "Distinct pattem of p53 phosphorylation in human tumors"Oncogene. 20. 3341-3347 (2001)

[Publications] Kanamori M: "Segregation analysis of gastric cancer in a Japanese population"Int J Human Genet. 1. 263-270 (2001)

[Publications] Sasaki Y: "Adenovirus-mediated transfer of the p53 family genes, p73 and p51/p63 induces cell cycle arrest and apoptosis in colorectal cancer cell lines : Potential application to gene therapy of colorectal cancer"Gene Therapy. 8. 1401-1408 (2001)

[Publications] Baba I: "Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-ras signaling pathway in human colon cancer cells"Cancer Res.. 60. 6886-6889 (2000)

[Publications] Ries S.: "Opposing effects of Ras on p53 : Transcriptional Activation of mdm2 and inductior of p19ARF"Cell. 103. 321-330 (2000)

[Publications] Shuang-Yin H.: "Functional evaluation of PTEN missense mutations using in vitro phosphoinositide phosphatase assay"Cancer Res. 60. 3147-3151 (2000)

[Publications] Keicho N: "Fine localization of a major disease-susceptibility locus for diffuse panbronchiolitis"Am J Hum Genet. 66. 501-507 (2000)

[Publications] Katai H: "Evaluation of the New International Union Against Cancer TNM staging for gastri carcinoma"Cancer. 88. 1796-1800 (2000)

[Publications] Nakamura K: "Morphometric analysis of regional lymph nodes with and without metastasis from early gastric cancinoma"Cancer. 88. 2438-2442 (2000)

[Publications] Ott I: "Reversible regulation of tissue factor-induced coagulation by glycosyl phosphatidylinositol-anchored tissue factor pathway inhibitor"Thromb Vasc Biol.. 20. 874-882 (2000)

笹月健彦国立国際医療センター, 研究所, 所長 (50014121)