The USC-JHU Cancer Epigenome Characterization Center

USC-JHU 癌症表观基因组表征中心

• 批准号: 7789003
• 负责人: STEPHEN B. BAYLIN
• 金额: $ 198.63万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-29 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7789003
• 关键词: Affect; Alkylating Agents; Atlases; Base Pairing; Biological; Clinical; CpG dinucleotide; DNA Methylation; DNA Sequence Rearrangement; Data; Deposition; Ensure; Epigenetic Process; Event; Gene Mutation; Genes; Genetic; Genome; Glioblastoma; Human; Individual; Link; MGMT gene; Malignant - descriptor; Malignant Neoplasms; Measures; Methylation; Mismatch Repair; Mutation; Outcome; Phase; Phenotype; Production; Quality Control; Resolution; Sampling; Sequence Analysis; Shotguns; Specialized Center; Techniques; bisulfite; cancer genome; epigenomics; insight; meetings; member; promoter; quality assurance; tumor; tumor progression

DESCRIPTION (provided by applicant): In the past two decades, it has become clear that cancer arises not only as a consequence of genetic events, such as mutations, copy number alterations, and sequence rearrangements, but also as a result of extensive changes to the epigenome. Epigenetic alterations contribute causally to the origin and malignant progression of cancer, and affect clinical outcome. The USC-JHU Cancer Epigenome Characterization Center specializes in the production and analysis of genome-scale cancer epigenetic data. During the pilot phase of The Cancer Genome Atlas, our center has been responsible for the production and deposition of all high-throughput epigenomic data within TCGA. A key outcome of the TCGA pilot was our finding of a link in glioblastoma multiforme between MGMT promoter methylation, treatment with alkylating agents, and a hypermutator phenotype associated with mismatch repair deficiency, an observation with potential clinical implications. For the next phase of TCGA, we propose the following three objectives. Objective 1 is to characterize the DNA methylation status of 27,578 CpG dinucleotides located in 14,495 gene promoters in at least 10,000 human cancer samples and 1,000 control samples using the lllumina Infinium DNA Methylation analysis platform. Objective 2 is to transition epigenomic data production in TCGA to whole genome shotgun bisulfite sequence analysis to provide single-base-pair resolution DNA methylation data for TCGA cancer samples. Objective 3 is to implement quality control and quality assurance measures to ensure that epigenomic data deposited for public dissemination meets rigorous standards. Our group has considerable expertise in cancer epigenomics, with two founders of the field of cancer epigenetics and with members who collectively have pioneered the majority of widely used DNA methylation analysis techniques, and who have provided many of the biological insights. Epigenomic data are a necessary component for a full understanding of the relationship between alterations in the cancer genome and the origin and clinical diversity of individual tumors.

描述（由申请人提供）：在过去的二十年里，人们已经清楚癌症的产生不仅是基因事件（例如突变、拷贝数改变和序列重排）的结果，而且也是表观基因组广泛变化的结果。表观遗传改变导致癌症的起源和恶性进展，并影响临床结果。 USC-JHU 癌症表观基因组表征中心专门从事基因组规模癌症表观遗传学数据的生成和分析。在癌症基因组图谱的试点阶段，我们的中心一直负责 TCGA 内所有高通量表观基因组数据的生成和存储。 TCGA 试点的一个关键成果是我们发现多形性胶质母细胞瘤中 MGMT 启动子甲基化、烷化剂治疗以及与错配修复缺陷相关的超变表型之间存在联系，这一观察结果具有潜在的临床意义。对于TCGA的下一阶段，我们提出以下三个目标。目标 1 是使用 lllumina Infinium DNA 甲基化分析平台表征至少 10,000 个人类癌症样本和 1,000 个对照样本中 14,495 个基因启动子中的 27,578 个 CpG 二核苷酸的 DNA 甲基化状态。目标 2 是将 TCGA 中的表观基因组数据生成转变为全基因组鸟枪法亚硫酸氢盐序列分析，为 TCGA 癌症样本提供单碱基对分辨率的 DNA 甲基化数据。目标 3 是实施质量控制和质量保证措施，确保供公众传播的表观基因组数据符合严格的标准。我们的团队在癌症表观基因组学方面拥有丰富的专业知识，有癌症表观遗传学领域的两位创始人，其成员共同开创了大多数广泛使用的 DNA 甲基化分析技术，并提供了许多生物学见解。表观基因组数据是充分了解癌症基因组变化与个体肿瘤的起源和临床多样性之间关系的必要组成部分。