Hox遺伝子群のメチル化異常と胃・大腸における発生部位特異的発癌・進展機構の解明

阐明Hox基因的异常甲基化以及胃和大肠中的位点特异性致癌和进展机制

• 批准号: 13877084
• 负责人: 山本 博幸
• 金额: $ 1.22万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Exploratory Research
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13877084/
• 关键词: Hox遺伝子; DNAメチレーション; 胃癌; 大腸癌; マイクロサテライト不安定性; CIMP

胃癌におけるゲノムワイドなメチル化異常(CpG island methylator phenotype ; CIMP)とマイクロサテライト不安定性(misrosatellite instability ; MSI)、局在との関連の有無を明らかにするために、hMLH1、p16^<INK4A>、MGMT、thrombos pondin-1、RAB-β、APC、p14^<ART>遺伝子のメチル化を、methylation-spcific PCRを用いて検討したところ、MSI-H胃癌の55%、MSS胃癌の18%がCIMP陽性で、前者に有意にCIMP陽性の頻度が高いことを明らかにした。また、hMLH1、p16遺伝子のメチル化は、有意に前庭部に多く認めた。簡便で再現性高くゲノムワイドなメチル化異常を検出できるmethylation sensitive-amplified fragment length polymorphism(MS-AFLP)法を用いて、胃・大腸癌のゲノムワイドなメチル化パターンを検討した。胃・大腸癌において、発生部位とMSIおよびCIMPの有無により、それぞれに特徴的なHox遺伝子群をはじめとする遺伝子メチル化パターンが明らかになった。以上により、特にHox遺伝子群のメチル化に注目することにより、胃・大腸癌における発生部位に特徴的な発癌・進展機構、更には、MSIおよびCIMPとの関連を解明できるものと考えられた。

Cancer of the stomach (CpG island methylator phenotype; CIMP) has a negative correlation (misrosatellite instability; MSI), and there is no indication that there are any signs of anxiety, hMLH1, p16 ^ & lt;INK4A>, MGMT, thrombos pondin-1, RAB- β, APC, p14 ^ & lt;ART&gt. Methylation-spcific PCR was used to treat gastric cancer, MSI-H gastric cancer was 55%, MSS gastric cancer was 18% CIMP, and the former was intentionally CIMP. Please, hMLH1, p16, and so on. The vestibule is intentional, and the vestibule is multi-functional. The method of methylation sensitive-amplified fragment length polymorphism (MS-AFLP) is often used in the treatment of gastric cancer. There are some subgroups of MSI cancer and CIMP in gastric cancer, such as gastric cancer, gastric cancer, gastric The above, special Hox subgroups focus on the mechanism of progression of gastric cancer, the specific location of gastric cancer, the mechanism of cancer progression, the diagnosis of gastric cancer, the mechanism of cancer progression, the mechanism of cancer progression, the diagnosis of gastric cancer, the mechanism of cancer progression, the diagnosis of gastric cancer, the mechanism of cancer progression, the mechanism of cancer progression, the diagnosis of gastric cancer, the mechanism of cancer progression, the diagnosis of gastric cancer, the mechanism of cancer progression

项目成果

Takefumi Kikuchi: "Inactivation of p57KIP2 by regional promoter hypermethylation and histone deacetylation in human tumors"Oncogene. 21. 2741-2749 (2002)

Takefum​​i Kikuchi：“人类肿瘤中区域启动子高甲基化和组蛋白脱乙酰化导致 p57KIP2 失活”癌基因。

Hiroyuki Yamamoto: "Microsatellite instability and gastrointestinal cancer"Gastrointestinal Function. 2. 121-129 (2002)

Hiroyuki Yamamoto：“微卫星不稳定性与胃肠癌”胃肠功能。

Hiroyuki Yamamoto: "Gastrointestinal cancer of the microsatellite mutator phenotype pathway"Journal of Gastroenterology. 37. 153-163 (2002)

Hiroyuki Yamamoto：“微卫星突变表型途径的胃肠癌”胃肠病学杂志。

Hiroyuki Yamamoto: "Differential involvement of the hypermethylator phenotype in hereditary and sporadic colorectal cancers with high-frequency microsatellite instability"Genes, Chromosomes and Cancer. 33. 322-325 (2002)

Hiroyuki Yamamoto：“高甲基化表型在具有高频微卫星不稳定性的遗传性和散发性结直肠癌中的不同参与”基因、染色体和癌症。

Hiroaki Takahashi: "Mucin phenotype and microsatellite instability in multiple early gastric cancers"International Journal of Cancer. 100. 419-424 (2002)

Hiroaki Takahashi：“多种早期胃癌中的粘蛋白表型和微卫星不稳定性”国际癌症杂志。