High throughput profiling of genomic methylation patterns

基因组甲基化模式的高通量分析

• 批准号: 7459062
• 负责人: TIMOTHY H BESTOR
• 金额: $ 20.13万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7459062
• 关键词: Breast Carcinoma; Chromosomes; Clinic; Clinical; Communities; Cytosine; DNA; DNA Library; DNA Sequence; Data; Diagnostic; Facility Construction Funding Category; Floods; Fractionation; Future; Genome; Genomics; Human; Malignant Neoplasms; Mammary Neoplasms; Methods; Methylation; Nature; Numbers; Pattern; Procedures; Purpose; Sampling; Source; anticancer research; base; cancer cell; cancer genome; cost; falls; improved; malignant breast neoplasm; new technology; novel; prognostic

DESCRIPTION (provided by applicant): The nature of the methylation abnormalities undergone by cancer cell genomes is of great importance to cancer research, but current methods of methylation profiling are biased, inefficient, very expensive, and provide only partial coverage. The new method presented here combines new methods of fractionation of DNA according to methylation status, new methods of genomic DNA library construction, and ultra-high throughput DNA sequencing to allow efficient whole-genome methylation profiling even when only nanogram amounts of DNA are available. As the cost of whole-genome methylation profiling falls and the procedure is automated, it is easy to imagine that whole-genome methylation profiles could be used in the clinic for diagnostic and prognostic purposes in the foreseeable future. Another very important result of this efficient new method of whole-genome methylation profiling will be the first complete description of the actual genomic methylation pattern in normal and cancer cells. This will greatly improve our understanding of the changes that methylation patterns undergo in mammary carcinoma. It is known that human DNA is modified by the methylation of cytosine bases, and that the patterns of methylated cytosines are abnormal in cancer. The extent of the abnormalities is not understood because methylation patterns are difficult to discern. We introduce new technologies that will profile the methylation pattern of the entire genome as a means to identify methylation pattern abnormalities that are associated with human breast cancer.

描述(申请人提供)：癌细胞基因组经历的甲基化异常的性质对癌症研究非常重要，但目前的甲基化分析方法有偏见、效率低、非常昂贵，并且只能提供部分覆盖。本文介绍的新方法结合了根据甲基化状态进行DNA分级的新方法、基因组DNA文库构建的新方法以及超高通量DNA测序，从而即使在仅有纳克量的DNA的情况下也可以进行高效的全基因组甲基化分析。随着全基因组甲基化图谱的成本下降和程序的自动化，很容易想象在可预见的未来，全基因组甲基化图谱可以用于临床诊断和预后目的。这种高效的全基因组甲基化图谱新方法的另一个非常重要的结果将是第一次完整地描述正常细胞和癌细胞的实际基因组甲基化模式。这将极大地提高我们对乳腺癌甲基化模式变化的理解。众所周知，人类DNA是通过胞嘧啶碱基的甲基化来修饰的，而在癌症中，甲基化的胞嘧啶模式是异常的。由于甲基化模式很难辨别，异常的程度尚不清楚。我们引入了新的技术，这些技术将描述整个基因组的甲基化模式，作为一种识别与人类乳腺癌相关的甲基化模式异常的手段。