1998 Fiscal Year Annual Research Report

日本人家族集積性胃癌の分離比分析(Segregationanalysis)と分子病理

Research Project

Project/Area Number	10151216
Research Institution	Hamamatsu University School of Medicine
Principal Investigator	椙村春彦浜松医科大学, 医学部, 教授 (00196742)
Co-Investigator(Kenkyū-buntansha)	金森雅夫浜松医科大学, 医学部, 助教授 (90127019)
Keywords	家族性胃ガン / E-カドヘリン / 分離比分析 / 組織型 / 分子疫学 / 遺伝子不安定性 / 多型
Research Abstract	家族集積性胃癌480のうち、家族の発症あるいは未発症時の年齢推定の可能であり、発端者の病理組織型が標準化されていた症例をその組織型により、未分化型156、分化型252例にわけた。Case Western Universityの分離比分析プログラムSAGEにより、その対応しうる遺伝様式を検定すると、未分化型において、常染色体劣性遺伝でないという仮説のみ棄却された。この解析ではprevalenceが0.331くらいの劣性遺伝子に関連することが推定された。また、未分化型、分化型ともにメンデルの法則にしたがうとして矛盾しない検定結果であった。これらの症例について、近年マオリ族で発見された、E-cadherinの生殖細胞変異(この場合は優勢遺伝子としてlinkageをおこす)を検索したところ、2例において、エクソン9のコドン415にlleから、Leuへのアミノ酸置換をともなう変異が認められた。E-cadherin遺伝子の検索はひきつづきおこなっており、その頻度などについての最終的結論はだせないが、べつの一施設と共同で行った結果では、13例中1例にprecursor部位の変化をみとめているのみであり、未分化型の家族性胃ガンのなかの1割以下であると考えられる。しかし、両変異とも現在まで世界でみいだされている10家系未満のprotein truncationをともなう生殖細胞変異ではなく、報告はこれまでないものの多型として比較的neutralなものである可能性があり、一般集団や散発性の胃ガン症例を検索中である。 E-cadherinのexon9は従来より日本人の胃ガンにおいて欠失のいわれている部位であり、この変異alleleで腫瘍内でのこっているかどうかも注目される。

Research Products

(16 results)

All Other

All Publications (16 results)

[Publications] Kohno,Takashi: "Genetic polymorphisms and alternative splicing of the hOGG1 gene,that involved in the repair of 8-hydroxyguanine in damaged DNA." Oncogene. 16. 3219-3226 (1998)
[Publications] Sugimura H: "Association of lle462Val(exon 7)polymorphism of cytochrome P450lA1 lung cancer in the Asian population: Further evidence from a case-control study in okinawa" Cancer Epidemiology,Biomarkers & Prevention. 7. 413-417 (1998)
[Publications] Yasuhisa Naito: "Collagen and elastin syntehsis by desmoid tumor in vitro." Pathology International. 48. 603-610 (1998)
[Publications] Hiroyuki Uchida: "Genetic alterations of mixed hyperplastic adenomatous polyps in the colon and rectum." Jpn.J.Cancer Res.89. 299-306 (1998)
[Publications] Tanaka M: "Interaction of EphB2-tyrosine kinase receptor and its ligand conveys dors alization signal in Xenopus laevis development." Oncogene. 17. 1509-1516 (1998)
[Publications] Kazuhiko Yasumi: "Tansforming Growth Factor beta type 2 receptor(TGFbRII)mutation in gastric lymphoma without mutator phenotype." Pathology International. 48. 134-137 (1998)
[Publications] Rong-Jun Guo: "Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer" Carcinogenesis. 19. 1539-1544 (1998)
[Publications] Kazuya Shinmura: "Infrequent mutations of the hOGG1 gene,that is involved in the excision of 8-hydroxyguanine in damaged DNA, in human gastric cancer." Japanese Journal of Cancer Research. 89. 825-8 (1998)
[Publications] Kiyokawa E: "Evidence That DOCK180 Up-regulates Signals from the Crkll-p130(Cas)Complex." J Biol Chem. 8;273(38). 24479-24484 (1998)
[Publications] Shinmura K: "RER phenotype and its associated mutations in familial gastric cancer." Carcinogenesis. 19. 247-251 (1998)
[Publications] Hiroyuki Konno: "Antitumor effect of a neutralizing antibody to vascular endotehlial growth factor on liver metastasis of endocrine neoplasm." Japanese Journal of Cancer Research. 89. 933-939
[Publications] Ying Wang: "Mutational analysis of multiple target genes in histologically heterogeneous gastric cancer with microsatellite instability." Japanese Journal of Cancer Research. 89. 1284-1291 (1998)
[Publications] Kiyokawa E: "Activation of Rac1 by a Crk SH3-binding protein, DOCK180." Genes Dev. 12(21). 3331-3336 (1998)
[Publications] Toshifumi Nakamura: "Hepatocellular Carcinoma in Type 1a Glycogen Storage Disease with Identification of a Glucose-6-Phosphatase Gene Mutation in One Family" Journal of Gastroenterology and Hepatology. (in press).
[Publications] Isogaki J: "Microsatellite instability and K-ras mutations in gastric adenomas, with reference to associated gastric cancers." Cancer Detection and Prevention. (in press).
[Publications] Shinmura K: "Familial gastric cancer: clinicopathological characteristics,RER phenotyp and germline p53 and E-cadherin mutations" Carcinogenesis. (in press).

1998 Fiscal Year Annual Research Report

日本人家族集積性胃癌の分離比分析(Segregationanalysis)と分子病理

Principal Investigator

椙村 春彦 浜松医科大学, 医学部, 教授 (00196742)

Research Products

[Publications] Kohno,Takashi: "Genetic polymorphisms and alternative splicing of the hOGG1 gene,that involved in the repair of 8-hydroxyguanine in damaged DNA." Oncogene. 16. 3219-3226 (1998)

[Publications] Sugimura H: "Association of lle462Val(exon 7)polymorphism of cytochrome P450lA1 lung cancer in the Asian population: Further evidence from a case-control study in okinawa" Cancer Epidemiology,Biomarkers & Prevention. 7. 413-417 (1998)

[Publications] Yasuhisa Naito: "Collagen and elastin syntehsis by desmoid tumor in vitro." Pathology International. 48. 603-610 (1998)

[Publications] Hiroyuki Uchida: "Genetic alterations of mixed hyperplastic adenomatous polyps in the colon and rectum." Jpn.J.Cancer Res.89. 299-306 (1998)

[Publications] Tanaka M: "Interaction of EphB2-tyrosine kinase receptor and its ligand conveys dors alization signal in Xenopus laevis development." Oncogene. 17. 1509-1516 (1998)

[Publications] Kazuhiko Yasumi: "Tansforming Growth Factor beta type 2 receptor(TGFbRII)mutation in gastric lymphoma without mutator phenotype." Pathology International. 48. 134-137 (1998)

[Publications] Rong-Jun Guo: "Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer" Carcinogenesis. 19. 1539-1544 (1998)

[Publications] Kazuya Shinmura: "Infrequent mutations of the hOGG1 gene,that is involved in the excision of 8-hydroxyguanine in damaged DNA, in human gastric cancer." Japanese Journal of Cancer Research. 89. 825-8 (1998)

[Publications] Kiyokawa E: "Evidence That DOCK180 Up-regulates Signals from the Crkll-p130(Cas)Complex." J Biol Chem. 8;273(38). 24479-24484 (1998)

[Publications] Shinmura K: "RER phenotype and its associated mutations in familial gastric cancer." Carcinogenesis. 19. 247-251 (1998)

[Publications] Hiroyuki Konno: "Antitumor effect of a neutralizing antibody to vascular endotehlial growth factor on liver metastasis of endocrine neoplasm." Japanese Journal of Cancer Research. 89. 933-939

[Publications] Ying Wang: "Mutational analysis of multiple target genes in histologically heterogeneous gastric cancer with microsatellite instability." Japanese Journal of Cancer Research. 89. 1284-1291 (1998)

[Publications] Kiyokawa E: "Activation of Rac1 by a Crk SH3-binding protein, DOCK180." Genes Dev. 12(21). 3331-3336 (1998)

[Publications] Toshifumi Nakamura: "Hepatocellular Carcinoma in Type 1a Glycogen Storage Disease with Identification of a Glucose-6-Phosphatase Gene Mutation in One Family" Journal of Gastroenterology and Hepatology. (in press).

[Publications] Isogaki J: "Microsatellite instability and K-ras mutations in gastric adenomas, with reference to associated gastric cancers." Cancer Detection and Prevention. (in press).

[Publications] Shinmura K: "Familial gastric cancer: clinicopathological characteristics,RER phenotyp and germline p53 and E-cadherin mutations" Carcinogenesis. (in press).

椙村春彦浜松医科大学, 医学部, 教授 (00196742)