Genomic and Epigenomic Profiling by MSNP

描述（由申请人提供）：DNA甲基化改变是癌细胞的标志，包括DNA甲基化获得和丧失在内的表观遗传畸变也是其他医学疾病的基础。这种表观遗传畸变被认为与癌症发生和发展中的遗传变化（如染色体丢失和获得）一致。在这项技术开发项目中，我们将开发并广泛验证一种具有成本效益的高分辨率和高通量方法，用于同时表征人类癌症中基因组范围内的遗传畸变和DNA甲基化改变。我们希望这种方法，我们验证MSNP（甲基化敏感的SNP阵列分析），将有助于回答基本问题，如DNA序列和甲基化模式之间的关系（遗传/表观遗传相互作用和等位基因特异性DNA甲基化）以及DNA甲基化和基因表达之间的关系，并且用于实现重要的医学目的，包括鉴定由DNA甲基化调节的肿瘤抑制基因和原癌基因，以及发现用于癌症诊断和检测的新的和稳健的标记物。改变的DNA甲基化是癌细胞的标志，DNA甲基化的获得和丧失也是其他医学疾病的基础。该项目旨在优化和验证一种名为MSNP的新方法，用于在正常和癌性人体组织中以高分辨率检测和绘制整个人类基因组的DNA甲基化。来自MSNP的数据有望揭示癌症的发病机制，并为癌症诊断和检测产生新的和强大的标志物。

DESCRIPTION (provided by applicant): Altered DNA methylation is a hallmark of cancer cells, and epigenetic aberrations including gains and losses of DNA methylation also underlie other medical disorders. Such epigenetic aberrations are thought to act in concert with genetic changes, such as chromosome losses and gains, in cancer initiation and progression. In this technology development project we will develop and extensively validate a cost-effective, high-resolution and high-throughput method for simultaneously characterizing genetic aberrations and alterations in DNA methylation genome wide in human cancers. We expect that this method, which we abbreviate MSNP (Methylation-sensitive SNP array analysis), will be useful both for answering fundamental questions such as the relationship between the DNA sequence and its pattern of methylation (genetic/epigenetic interactions and allele-specific DNA methylation) and the relationship between DNA methylation and gene expression, and for achieving important medical objectives including identifying tumor suppressor genes and proto-oncogenes regulated by DNA methylation and finding new and robust markers for cancer diagnosis and detection. Altered DNA methylation is a hallmark of cancer cells, and gains and losses of DNA methylation also underlie other medical disorders. This project is designed to optimize and validate a new method, called MSNP, for detecting and mapping DNA methylation at high resolution across the entire human genome in both normal and cancerous human tissues. Data from MSNP are expected to shed light on cancer pathogenesis and produce new and robust markers for cancer diagnosis and detection.