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. ? ? ? ?
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