We propose to operate a Genome Characterization Center for The Cancer Genome Atlas (TCGA) of the National Cancer Institute. Our goal is to characterize the genomes and transcriptomes of 10,000 human cancers over 5 years, together with the collaborators of TCGA Research Network. Given the ongoing revolution in genome analysis, our Center will transition from current-generation microarray technologies to next-generation sequencing technologies for cancer genome characterization. We will accomplish this by benchmarking the next-generation technologies against state-of-the-art array technologies used in the pilot project of TCGA. Our Center is uniquely qualified for this effort, because of our expertise in next-generation sequencing as well as current-generation microarray production and technology development, our knowledge and demonstrated accomplishments in cancer genomics, and our commitment to and experience with multi-institutional collaborations including the pilot project of TCGA. Specifically, we intend to accomplish the following aims for TCGA:
Aim 1. Using microarray technologies: Characterize DNA and RNA from 2000 cancer samples and appropriate controls during year 1.
Aim 2. Using next-generation sequencing: (i) Perform direct comparison and validation of the three alternative platforms during year 1, by characterizing DNA from 300 cancer/normal sample pairs and RNA from 100 cancer samples. (ii) Select the most cost-effective sequencing platform at the end of year 1, based on the results and in conjunction with NCI staff. (iii) Implement this sequencing platform to characterize DNA and RNA from 2000 cancer samples and appropriate controls in Years 2-5. (iv) Continue to decrease cost and increase resolution of genomic analysis.

Public Health Relevance

Cancer is a genomic disease, caused by somatic and germ-line alterations in DNA and RNA. By discovering and enumerating these alterations, we can improve the diagnosis and treatment of cancer: this is the goal of The Cancer Genome Atlas. Our proposed Genome Characterization Center could contribute significantly to TCGA by advancing genomic technology and by rapidly accomplishing cancer genome discoveries.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Resource-Related Research Projects--Cooperative Agreements (U24)
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Special Emphasis Panel (ZCA1-SRLB-U (O1))
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Tarnuzzer, Roy W
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Broad Institute, Inc.
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Ding, Li; Bailey, Matthew H; Porta-Pardo, Eduard et al. (2018) Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics. Cell 173:305-320.e10
Seiler, Michael; Peng, Shouyong; Agrawal, Anant A et al. (2018) Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types. Cell Rep 23:282-296.e4
Liu, Yang; Sethi, Nilay S; Hinoue, Toshinori et al. (2018) Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas. Cancer Cell 33:721-735.e8
Jayasinghe, Reyka G; Cao, Song; Gao, Qingsong et al. (2018) Systematic Analysis of Splice-Site-Creating Mutations in Cancer. Cell Rep 23:270-281.e3
Saltz, Joel; Gupta, Rajarsi; Hou, Le et al. (2018) Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images. Cell Rep 23:181-193.e7
Ellrott, Kyle; Bailey, Matthew H; Saksena, Gordon et al. (2018) Scalable Open Science Approach for Mutation Calling of Tumor Exomes Using Multiple Genomic Pipelines. Cell Syst 6:271-281.e7
Campbell, Joshua D; Yau, Christina; Bowlby, Reanne et al. (2018) Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas. Cell Rep 23:194-212.e6
Gao, Qingsong; Liang, Wen-Wei; Foltz, Steven M et al. (2018) Driver Fusions and Their Implications in the Development and Treatment of Human Cancers. Cell Rep 23:227-238.e3
Thorsson, V├ęsteinn; Gibbs, David L; Brown, Scott D et al. (2018) The Immune Landscape of Cancer. Immunity 48:812-830.e14
Radovich, Milan; Pickering, Curtis R; Felau, Ina et al. (2018) The Integrated Genomic Landscape of Thymic Epithelial Tumors. Cancer Cell 33:244-258.e10

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