Entwicklung von Oligonukleotid-Arrays für die Charakterisierung von genomischen DNA-Methylierungsmustern in Tumoren

开发用于表征肿瘤基因组 DNA 甲基化模式的寡核苷酸阵列

• 批准号: 5394392
• 负责人: Dr. Jörg Hoheisel
• 金额: --
• 依托单位: Abteilung Funktionelle Genomanalyse
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2004-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5394392?language=en
• 关键词: Entwicklung; von; Oligonukleotid; Arrays; die

Changes in genomic DNA methylation patterns are one of the earliest and most consistent features of tumourigenesis. However, very little is known about the nature of these changes and their role in cellular transformation. Progress in the field has been hampered by the unavailability of methods for genomic epigenetic profiling. Using chronic lymphocytic leukemia as a model system, we have shown previously that aberrant DNA methylation profiles can be used as a valuable marker for clinical tumour characterisation. In independent experiments, we have established a method for the detection of single-base polymorphisms on oligonucleotide microarrays. Because the methylation status of a defined nucleotide can also be interpreted to represent a single nucleotide polymorphism, we propose to utilise the latter technology for a genome-wide, gene-specific analysis of DNA methylation patterns. This approach will result in a detailed characterisation of genomic methylation patterns. The data will be evaluated together with the available clinical data and results from trancriptional profiling. Our results will allow fundamental insights into the role of DNA methylation during tumouresis and will provide the foundation for an epigenetic classification of tumours.

基因组DNA甲基化模式的变化是肿瘤发生的最早和最一致的特征之一。然而，人们对这些变化的性质及其在细胞转化中的作用知之甚少。由于缺乏基因组表观遗传谱分析方法，这一领域的进展受到阻碍。使用慢性淋巴细胞白血病作为模型系统，我们之前已经表明异常DNA甲基化谱可以用作临床肿瘤特征的有价值标记。在独立实验中，我们建立了一种检测寡核苷酸微阵列上单碱基多态性的方法。由于特定核苷酸的甲基化状态也可以被解释为代表单核苷酸多态性，因此我们建议利用后一种技术进行全基因组DNA甲基化模式的基因特异性分析。这种方法将导致基因组甲基化模式的详细特征。这些数据将与现有的临床数据和转录谱分析结果一起进行评估。我们的研究结果将有助于深入了解DNA甲基化在肿瘤发生过程中的作用，并为肿瘤的表观遗传分类提供基础。