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Cancer Genome Characterization using Gene Expression and DNA Copy Number Analysis

使用基因表达和 DNA 拷贝数分析进行癌症基因组表征

基本信息

批准号：
7908252
负责人：
CHARLES M. PEROU
金额：
$ 30万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7908252
关键词：
Atlases Back Biological Assay Breast Cancer Etiology Classification Clinical Color Complex Cost Savings Custom DNA Microarray Chip DNA Resequencing DNA copy number Data Data Analyses Data Set Development Disease Dyes Evaluation Gene Expression Gene Expression Microarray Analysis Gene Expression Profiling Gene Proteins Genes Genetic Genomics Head and neck structure Human Human Genome Infectious Agent Informatics Lead Link Malignant Neoplasms Malignant neoplasm of lung Mammary Neoplasms Measures Messenger RNA MicroRNAs Microarray Analysis Microfabrication Molecular Profiling Mutation Nucleic Acids Optics Outcome Patients Pattern Performance Price Publications Sampling Site Somatic Mutation Specimen Stratification Techniques Technology Testing Tumor Biology Tumor Subtype Tumor Suppressor Genes Validation Variant Viral assay development base cancer genome clinically relevant comparative genomic hybridization cost data mining density design experience flexibility genome-wide high throughput technology interest novel pathogen protein function research study success tool tumor

项目摘要

DESCRIPTION (provided by applicant): With the publication of the human genome's complete sequence, in combination with advances in optics, microfabrication and computing, many of the previously described cancer causing genetic aberrations can now be characterized, or profiled, using high-density technologies. Although there has been a plethora of different assays/platforms developed, two platforms have been the most extensively utilized and include mRNA/gene expression profiling (DNA microarrays) and array-based Comparative Genomic Hybridization (aCGH microarrays) for measuring DNA copy number abnormalities. While these platforms were partially developed in academic labs, the commercial development of gene and aCGH microarrays has resulted in competitive pricing, high array quality, flexibility for the refinement of probes, and development of a large range of analytic tools. Our own experience in the development of these assays and in the application of them to the study of breast and lung cancer, has lead to the identification of novel subtypes of tumors and to the identification of a new tumor suppressor gene. This leads us to propose to use DNA microarray and aCGH arrays to characterize tumors provided through the Cancer Genome Characterization Centers. Specifically, we propose to characterize the provided human tumors using Agilent Technologies Inc. produced arrays with up to 244,000 features and to perform 1) gene expression microarray analysis containing all known human genes, 2) DNA microarrays containing approximately 1000 different viral and bacterial pathogens to test for the presence of infectious agents, 3) microarrays containing all known human MicroRNA, and 4) aCGH microarrays to determine DNA copy number changes. Our group has demonstrated expertise with all of these data types and with the analysis of these data. Importantly, we have also developed new data mining techniques that have allowed for integration and cross-validation of these comprehensive genomic data sets.

描述（由申请人提供）：随着人类基因组完整序列的公布，结合光学、微加工和计算技术的进步，许多先前描述的致癌基因畸变现在可以使用高密度技术进行表征或分析。虽然已经开发了大量不同的检测/平台，但有两种平台得到了最广泛的应用，包括用于测量DNA拷贝数异常的mRNA/基因表达谱（DNA微阵列）和基于阵列的比较基因组杂交（aCGH微阵列）。虽然这些平台部分是在学术实验室开发的，但基因和aCGH微阵列的商业开发已经带来了具有竞争力的价格，高阵列质量，探针改进的灵活性以及大范围分析工具的开发。我们在开发这些检测方法以及将其应用于乳腺癌和肺癌研究方面的经验，已经导致鉴定出新的肿瘤亚型和鉴定出新的肿瘤抑制基因。这导致我们提出使用DNA微阵列和aCGH阵列来表征癌症基因组表征中心提供的肿瘤。具体来说，我们建议使用安捷伦技术公司生产的多达244,000个特征的阵列来表征所提供的人类肿瘤，并执行1)包含所有已知人类基因的基因表达微阵列分析，2)包含大约1000种不同病毒和细菌病原体的DNA微阵列来测试感染因子的存在，3)包含所有已知人类MicroRNA的微阵列，以及4)aCGH微阵列来确定DNA拷贝数的变化。我们的团队已经展示了对所有这些数据类型以及对这些数据的分析的专业知识。重要的是，我们还开发了新的数据挖掘技术，可以对这些全面的基因组数据集进行整合和交叉验证。