Novel approach to whole genome methylation profiling of breast cancer
乳腺癌全基因组甲基化分析的新方法
基本信息
- 批准号:7471745
- 负责人:
- 金额:$ 11.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-06-01 至 2009-11-30
- 项目状态:已结题
- 来源:
- 关键词:AreaAutomobile DrivingBiological MarkersChromosomal RearrangementDNADNA SequenceDNA Sequence RearrangementDataEpigenetic ProcessEventFractionationGenesGenomeGenomicsGoalsHypermethylationMalignant NeoplasmsMammary NeoplasmsMapsMentorsMessenger RNAMethodsMethylationNaturePatternPhasePlayProcessProto-OncogenesRecurrenceRegulationRepetitive SequenceResearch PersonnelRoleSamplingSampling StudiesStagingTechniquesTechnologyThinkingTumor Suppressor GenesTumor Suppressor Proteinsanticancer researchbasecancer cellcostdemethylationinsightmRNA Expressionmalignant breast neoplasmnovelnovel strategiesprogramspromoterresearch studytumor
项目摘要
DESCRIPTION (provided by applicant): Understanding the role of methylation abnormalities undergone by cancer cell genomes is of great importance to cancer research and treatment; however, one major limitation has been the lack of a method for analyzing the methylation patterns of the entire genome simultaneously in a rapid, cost-effective manner. For instance, array based techniques cannot be used to reveal the methylation status of repetitive elements, which are hypothesized to play a key function in the altered expression patterns and rearrangements found in cancer cells. In particular, the role of methylation in breast cancer is still poorly understood; both hypermethylation of tumor suppressor gene promoters and global hypomethylation of the genome are thought to play significant early roles. The novel method presented here combines new techniques of fractionation of DNA according to methylation status and ultra-high throughput DNA sequencing using "Next- Gen" DNA sequencing technologies to allow efficient whole-genome methylation profiling even when only microgram amounts of DNA are available. We will use this technology to examine the complete genomic methylation status of a panel of breast cancer samples and study how these patterns correlate with various factors such as survival and recurrence to develop methylation profiles as a potentially powerful biomarker. We will use this data as a platform to elucidate the role methylation plays in breast cancer as a regulatory agent. We will determine if the hypomethylationthat characterizes breast cancer is a stochastic or directed process and examine whether tumor suppressor hypermethylation is a key factor in breast cancer or if this is solely a sporadic event. We will also examine the effects of methylation on hotspots for chromosomal rearrangements, which are commonly found in breast cancer. This project, via a whole genome methylation profiling method that is unbiased and capable of investigating the methylation status of all sequences including the repeated sequences known to be demethylated in breast cancer, will provide a first look into the complete methylation landscape of breast cancer and provide new insights into epigenetic abnormalities in cancer.
描述(申请人提供):了解癌细胞基因组甲基化异常的作用对癌症研究和治疗具有重要意义;然而,一个主要的限制是缺乏一种方法来分析整个基因组的甲基化模式,同时在一个快速的,具有成本效益的方式。例如,基于阵列的技术不能用于揭示重复元件的甲基化状态,而重复元件被假设在癌细胞中发现的表达模式改变和重排中起关键作用。特别是,甲基化在乳腺癌中的作用仍然知之甚少;肿瘤抑制基因启动子的高甲基化和基因组的整体低甲基化被认为在早期发挥了重要作用。本文提出的新方法结合了根据甲基化状态分离DNA的新技术和使用“下一代”DNA测序技术的超高通量DNA测序,即使只有微克量的DNA可用,也可以实现高效的全基因组甲基化分析。我们将使用这项技术来检查一组乳腺癌样本的完整基因组甲基化状态,并研究这些模式如何与生存和复发等各种因素相关,以开发甲基化谱作为潜在的强大生物标志物。我们将利用这些数据作为平台来阐明甲基化作为一种调节剂在乳腺癌中所起的作用。我们将确定乳腺癌特征的低甲基化是随机的还是定向的过程,并研究肿瘤抑制因子高甲基化是否是乳腺癌的关键因素,还是仅仅是一个偶发事件。我们还将研究甲基化对染色体重排热点的影响,这在乳腺癌中很常见。该项目通过一种无偏倚的全基因组甲基化分析方法,能够调查所有序列的甲基化状态,包括已知在乳腺癌中去甲基化的重复序列,将为乳腺癌的完整甲基化景观提供第一个视角,并为癌症的表观遗传异常提供新的见解。
项目成果
期刊论文数量(0)
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John R Edwards其他文献
John R Edwards的其他文献
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{{ truncateString('John R Edwards', 18)}}的其他基金
Single-cell approaches to probe the function of the unique neuronal epigenome
单细胞方法探测独特神经元表观基因组的功能
- 批准号:
10440762 - 财政年份:2022
- 资助金额:
$ 11.41万 - 项目类别:
Single-cell approaches to probe the function of the unique neuronal epigenome
单细胞方法探测独特神经元表观基因组的功能
- 批准号:
10578749 - 财政年份:2022
- 资助金额:
$ 11.41万 - 项目类别:
Computational modeling of DNA methylation-mediated gene regulation
DNA甲基化介导的基因调控的计算模型
- 批准号:
9896942 - 财政年份:2019
- 资助金额:
$ 11.41万 - 项目类别:
Computational modeling of DNA methylation-mediated gene regulation
DNA甲基化介导的基因调控的计算模型
- 批准号:
10018936 - 财政年份:2019
- 资助金额:
$ 11.41万 - 项目类别:
Computational modeling of DNA methylation-mediated gene regulation
DNA甲基化介导的基因调控的计算模型
- 批准号:
10405488 - 财政年份:2019
- 资助金额:
$ 11.41万 - 项目类别:
MODELING DNA METHYLATION'S ROLE IN GENE REGULATION
模拟 DNA 甲基化在基因调控中的作用
- 批准号:
8759963 - 财政年份:2014
- 资助金额:
$ 11.41万 - 项目类别:
MODELING DNA METHYLATION'S ROLE IN GENE REGULATION
模拟 DNA 甲基化在基因调控中的作用
- 批准号:
8899611 - 财政年份:2014
- 资助金额:
$ 11.41万 - 项目类别:
A MACHINE LEARNING APPROACH FOR FINE-SCALE GENOME WIDE DNA METHYLATION ANALYSIS
用于精细规模全基因组 DNA 甲基化分析的机器学习方法
- 批准号:
8229567 - 财政年份:2012
- 资助金额:
$ 11.41万 - 项目类别:
Novel approach to whole genome methylation profiling of breast cancer
乳腺癌全基因组甲基化分析的新方法
- 批准号:
8013458 - 财政年份:2008
- 资助金额:
$ 11.41万 - 项目类别:
Novel approach to whole genome methylation profiling of breast cancer
乳腺癌全基因组甲基化分析的新方法
- 批准号:
8239536 - 财政年份:2008
- 资助金额:
$ 11.41万 - 项目类别:
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