The TCGA Cancer Genome Characterization Center at MSKCC

描述（由申请人提供）：位于MSKCC的TCGA癌症基因组表征中心（本文指定为MSK-CGCC）将提供基因表达（全转录本，外显子水平和microRNA）和基因组收益和损失（全基因组和高分辨率癌症基因中心）的综合分析，并将执行高水平的生物信息学分析，以确定由TCGA基因组测序中心重测序的候选基因和新的候选基因间重排。具体而言，MSK-CGCC将满足RFA的三个目标如下：目标1：应用已建立的综合高通量技术。我们将在当前Affymetrix U133 Plus阵列上进行基因表达谱分析，并在Agilent 244k CGH阵列上进行增益和损失谱分析。鉴于我们的微阵列设备已经具有很高的容量，MSK-CGCC将准备立即进行预期的第一年1000个样品的吞吐量。目的2：提高大规模基因组表征平台的性能。这些标准平台将通过增强基因组覆盖率和检测其他类型的基因组改变而得到扩展。因此，经过仔细的评估和验证，Affymetrix U133 Plus阵列将通过实施（将提供异常剪接模式和易位融合转录物的数据）和使用Agilent microRNA阵列来扩展，后者将在连续几年中通过基于迄今为止组装的最全面的人类microRNA库的更新设计来增强。安捷伦244k CGH阵列将通过设计互补的定制安捷伦阵列进行扩展，该阵列基于以癌症基因为中心的平纹策略，最适合于检测与增益或损失相关的基因融合。目标3：建立内聚分析和数据挖掘工具。MSK-CGCC生物信息学团队将使用最先进的方法进行原始数据处理和质量控制，以确保所有发布的数据都得到很好的验证。他们还将进行各种高级分析和综合分析，以获得TCGA基因组测序中心测序感兴趣的基因和基因组区域的优先列表。

DESCRIPTION (provided by applicant): The TCGA Cancer Genome Characterization Center at MSKCC (designated herein MSK-CGCC) will provide comprehensive profiling of gene expression (whole transcript, exon-level, and microRNA) and of genomic gains and losses (whole genome, and high resolution cancer gene-centered) and will perform high level bioinformatic analyses to identify candidate genes for resequencing by the TCGA Genome Sequencing Centers and novel candidate intergenic rearrangements. Specifically, the MSK-CGCC will meet the three objectives of the RFA as follows: Objective 1: Application of established comprehensive high-throughput technologies. We will perform gene expression profiling on the current Affymetrix U133 Plus arrays and profiling of gains and losses on Agilent 244k CGH arrays. Given the already high capacity of our microarray facility, the MSK-CGCC will be ready to proceed immediately with the expected first year throughput of 1000 samples in this objective. Objective 2: Improve performance of large-scale genomic characterization platforms. These standard platforms will be extended by enhancement of genome coverage and detection of additional types of genomic alterations. Thus, Affymetrix U133 Plus arrays will be extended by the implementation, following careful evaluation and validation, of the new Affymetrix Exon arrays (that will provide data on aberrant splicing patterns and translocation fusion transcripts) and by the use of Agilent microRNA arrays, the latter to be enhanced in successive years by updated designs based on the most comprehensive library of human microRNAs assembled to date. The Agilent 244k CGH arrays will be extended by the design of a complementary custom Agilent array based on a cancer gene-centered tiling strategy optimally suited for the detection of gene fusions associated with gains or losses. Objective 3: Establish cohesive analysis and data mining tools. The MSK-CGCC bioinformatics team will use state-of-the-art methods for raw data processing and quality control to ensure that all released data are well validated. They will also perform a variety of higher level analyses and integrated analyses to derive prioritized lists of genes and genomic regions of interest for sequencing by the TCGA Genome Sequencing Centers.