[癌症的表观基因组诊断——关注结直肠癌全基因组DNA甲基化诊断预测抗egfr抗体治疗敏感性]。

Q4 Medicine Japanese Journal of Cancer and Chemotherapy Pub Date : 2024-11-01
Chikashi Ishioka, Kota Ouchi, Shonosuke Wakayama, Shin Takahashi
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引用次数: 0

摘要

DNA甲基化和组蛋白乙酰化等表观遗传调控机制在基因组水平上通过调控基因表达来控制各种生物现象具有重要意义。它们是根据环境因素而变化的可逆系统。表观遗传异常与各种疾病的发病有关,包括发育和衰老异常、神经系统疾病和恶性肿瘤。DNA甲基化异常是结直肠癌发生发展过程中一个重要的表观遗传变化。肿瘤组织中的DNA甲基化主要发生在基因启动子区域的CpG岛上,通过负抑制转录使基因功能失活。CpG岛甲基化表型(CpG island methylator phenotype, CIMP)是与DNA甲基化相关的结直肠癌的重要致癌机制,约占所有结直肠癌的20%。当标记基因组有一定比例或更多的甲基化时,通常判断CIMP为阳性,目前已有许多CIMP标记的报道。然而,目前还没有确定的标记物可以通过全基因组DNA甲基化对结直肠癌进行分类。我们开发了一种评估全基因组DNA甲基化状态的新方法,并获得了药物批准,作为一种新的体外诊断药物,用于预测结直肠癌患者对抗egfr抗体药物的敏感性。
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[Epigenome Diagnosis of Cancer-Focusing on Genome-Wide DNA Methylation Diagnosis of Colorectal Cancer for Predicting Sensitivity of Anti-EGFR Antibody Treatment].

Epigenetic regulation mechanisms such as DNA methylation and histone acetylation are important for controlling various biological phenomena by regulating gene expression at the genome level. They are reversible systems that change depending on environmental factors. Epigenetic abnormalities are associated with the onset of various diseases, including developmental and aging abnormalities, neurological disorders, and malignant tumors. Aberrant DNA methylation is an important epigenetic change in the development and progression of colorectal cancer. DNA methylation in tumor tissues occurs mainly in CpG islands in the promoter regions of genes and inactivates gene functions by negatively suppressing transcription. CpG island methylator phenotype(CIMP)is an important carcinogenic mechanism of colorectal cancer related to DNA methylation and is involved in approximately 20% of all colorectal cancers. CIMP is generally judged to be positive when a certain percentage or more of the marker gene set is methylated, and many CIMP markers have been reported so far. However, no established marker has been set to classify colorectal cancer by genome-wide DNA methylation. We developed a new method to assess genome-wide DNA methylation status and obtained pharmaceutical approval as a new in vitro diagnostic drug to predict sensitivity to anti-EGFR antibody drugs in colorectal cancer.

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