Development of high sensitive screening method by fecal DNA test targeting colorectal cancer; pancreatic and binary tract cancers

开发针对结直肠癌的粪便DNA检测高灵敏度筛查方法；

• 批准号: 17591403
• 负责人: MATSUBARA Nagahide
• 金额: $ 2.11万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591403/
• 关键词: gastroenterological cancer; carcinogenesis; genetic alteration; epigenetic alteration; colorectal cancer; gastric cancer; esophageal cancer; mi crosatel1ite instability; 遺伝子; 癌; 診断; 臨床

We have been studied molecular mechanisms of gastrointestinal carcinogenesis and cancer progression. Recently not only genetic, including mutations and deletions, but also epigenetic alterations are involved in many types of carcinogenesis. The most typical epigenetic alteration is the promoter hypermethylation, which causes the silencing of the gene. DNA methylation occurs preferentially within dense clusters of CpG sites know as CpG islands. Therefore reference is made to a CpG island methylator phenotype (CIMP). we classified colorectal cancer by mutational status of KRAS and BRAF, and showed close correlation to the methylation status of the multiple promoter methylation in colorectal cancer (Journal of Clinical Oncology). More recently, we investigated the overall relationship between activation of RAS-RAF signaling pathway and global hypermethylation in a large panel of methylation markers that included both CIMP-related and unrelated loci. Interestingly, we found that aberrant DNA methylation is only a disease of older individuals with MSI-H but in associated with all subsets of colorectal cancers. Herein, we found that epigenetic markers can be used for the screening of colorectal cancer if we chose the correct methylation marker. We also developed a novel method to detect cancer-derived methylation in the exfoliated DNA from cancer in feces and applied several patents. We have also focused on the cancer with poor prognosis mainly due to the difficulty in screening and early diagnosis, such as pancreatic and hepato-biliary tract cancers.

我们已经研究了胃肠道癌发生和癌症进展的分子机制。近年来，许多类型的癌症发生不仅涉及基因（包括突变和缺失），而且还涉及表观遗传学改变。最典型的表观遗传学改变是启动子高甲基化，其导致基因沉默。DNA甲基化优先发生在称为CpG岛的CpG位点的密集簇内。因此，参考CpG岛甲基化表型（CIMP）。我们通过KRAS和BRAF的突变状态对结肠直肠癌进行分类，并显示与结肠直肠癌中多启动子甲基化的甲基化状态密切相关（临床肿瘤学杂志）。最近，我们研究了RAS-RAF信号通路的激活与包括CIMP相关和不相关基因座的大组甲基化标记物中的全局超甲基化之间的总体关系。有趣的是，我们发现异常DNA甲基化只是MSI-H老年人的一种疾病，但与所有结直肠癌亚群相关。在此，我们发现，如果我们选择正确的甲基化标记，表观遗传标记可以用于结直肠癌的筛查。我们还开发了一种新的方法来检测粪便中癌症脱落DNA中的癌源性甲基化，并申请了多项专利。我们还关注了预后不良的癌症，主要是由于筛查和早期诊断的困难，如胰腺癌和肝胆道癌。

项目成果

核酸増幅反応を行うための生物学的資料の処理方法

用于核酸扩增反应的生物材料的处理方法

• 发表时间: 2005

Role of O6-methylguanine-DNA methyltransferase and effect of O6-benzylguanine on the anti-tumor activity of cis-diaminedichloroplatinum(II) in oral cancer cell lines

• DOI: 10.1016/j.oraloncology.2005.05.011
• 发表时间: 2005-11-01
• 期刊: ORAL ONCOLOGY
• 影响因子: 4.8
• 作者: Maki, Y;Murakami, J;Kishi, K
• 通讯作者: Kishi, K

消化器中の新生物の検出方法

如何检测消化道肿瘤

• 发表时间: 2005

Methylatio profiles of genes utilizing newly developed CpG island methylation microarray on colorectal cancer patients.

利用新开发的 CpG 岛甲基化微阵列对结直肠癌患者进行基因甲基化谱分析。

• 发表时间: 2005
• 期刊: Nucleic Acids Res 33
• 作者: Ikegami T.;Soejima Y.;Taketomi A.;Yoshizumi T.;Kayashima H.;Uchiyama H.;Shimada M.;Maehara Y.;Naoki Kimura et al.
• 通讯作者: Naoki Kimura et al.

核酸修飾前の検体の前処理方法

核酸修饰前标本的预处理方法

• 发表时间: 2005