Cancer Genomics Center

癌症基因组中心

• 批准号: 7908618
• 负责人: Raju S. Kucherlapati
• 金额: $ 64.93万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 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/7908618
• 关键词: Atlases; Award; Boston; DNA Resequencing; Data; Data Analyses; Data Storage and Retrieval; Electrophoresis; Gene Expression Profiling; Genes; Goals; Grant; Informatics; Libraries; Loss of Heterozygosity; Methodology; Methods; Molecular Profiling; Oligonucleotide Microarrays; Patients; Process; RNA; Research Infrastructure; Sampling; Stratification; Time; base; cancer Biomedical Informatics Grid; cancer genome; cancer genomics; comparative genomic hybridization; cost; density; improved; interest; member; serial analysis of gene expression; tool; tumor; tumor initiation

DESCRIPTION (provided by applicant): We are seeking support to establish a Cancer Genome Characterization Center in Boston. The goal of the proposed effort is to analyze 3000 tumor samples over a three-year period of time and identify a set of genes that can be resequenced by the members of The Cancer Genome Atlas (TCGA) project. It is well established that regions of the cancer genome that are amplified or show loss of heterozygosity or deletion harbor genes that are important for tumor initiation and progression. We propose to identify such regions in the cancer genome by conducting array comparative genomic hybridization (aCGH). Based upon detailed comparisons of many different platforms we have chosen to use the high-density Agilent oligonucleotide arrays for our studies. We already have the ability to have a throughput of processing a thousand samples during the first year of the proposed grant. We plan to continually improve the processes and reduce the cost of obtaining these data during the remaining portion of the grant period. The regions of amplification or deletion harbor many genes. An optimal way to identify the critical gene within these intervals is through gene expression profiling of RNA from tumors. There are several platforms for expression profiling and one of the most informative methods is through the use of a platform called Serial Analysis of Gene Expression (SAGE). Although SAGE is powerful it involves construction of "Tag" libraries and sequencing these libraries. The cost of sequencing each of the libraries with conventional methodologies is prohibitive. We have developed and validated a method called "Polony" sequencing that is capable of providing highly accurate sequencing information at a small fraction of cost required for conventional electrophoresis or pyrosequencing based methods. We have already successfully used this method to obtain expression profiles from small amount of polyA RNA and we propose to utilize this method to generate data from 3000 tumor samples in the proposed grant period. During the first six months we will implement this method and will be able to achieve the goal of generating data at the rate of 1,000 tumors/year. We also propose to use powerful informatics tools that we have developed or implemented to integrate the aCGH and expression profiling data and extract a list of most interesting genes for resequencing. We have established an award winning IT infrastructure that will be deployed for LIMS, data storage, data retrieval, data analysis and interface with caBIG. Our proposed approach also has the ability to generate additional useful data for tumor and patient stratification.

描述（由申请人提供）：我们正在寻求支持，以建立一个癌症基因组表征中心在波士顿。这项计划的目标是在三年的时间内分析3000个肿瘤样本，并确定一组可以由癌症基因组图谱（TCGA）项目成员重新测序的基因。已经确定的是，扩增或显示杂合性丢失或缺失的癌症基因组区域含有对肿瘤起始和进展重要的基因。我们建议通过进行阵列比较基因组杂交（aCGH）来识别癌症基因组中的这些区域。基于对许多不同平台的详细比较，我们选择使用高密度Agilent寡核苷酸阵列进行研究。我们已经有能力在拟议拨款的第一年处理1000个样本。我们计划继续改进流程，并在赠款期的剩余部分降低获取这些数据的成本。扩增或缺失的区域包含许多基因。在这些间隔内鉴定关键基因的最佳方法是通过肿瘤RNA的基因表达谱。有几种表达谱分析平台，其中一种信息量最大的方法是使用称为基因表达系列分析（SAGE）的平台。虽然SAGE是强大的，但它涉及“标签”文库的构建和对这些文库的测序。用常规方法对每个文库测序的成本过高。我们已经开发并验证了一种称为“Polony”测序的方法，该方法能够以基于常规电泳或焦磷酸测序的方法所需的一小部分成本提供高度准确的测序信息。我们已经成功地使用这种方法从少量的polyA RNA中获得表达谱，我们建议利用这种方法在建议的资助期内从3000个肿瘤样本中生成数据。在前六个月，我们将实施这种方法，并将能够实现以每年1,000个肿瘤的速度生成数据的目标。我们还建议使用我们已经开发或实施的强大的信息学工具来整合aCGH和表达谱数据，并提取一系列最有趣的基因进行重测序。我们已经建立了一个屡获殊荣的IT基础设施，将部署LIMS，数据存储，数据检索，数据分析和与caBIG的接口。我们提出的方法还能够为肿瘤和患者分层生成额外有用的数据。

项目成果

A developmental taxonomy of glioblastoma defined and maintained by MicroRNAs.

• DOI: 10.1158/0008-5472.can-10-4117
• 发表时间: 2011-05-01
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Kim TM;Huang W;Park R;Park PJ;Johnson MD
• 通讯作者: Johnson MD

ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking.

• DOI: 10.1093/bioinformatics/btq170
• 发表时间: 2010-06-15
• 期刊: Bioinformatics (Oxford, England)
• 作者: Wilkerson MD;Hayes DN
• 通讯作者: Hayes DN