Center for Advanced Multi-Omic Characterization of Cancer

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PROJECT SUMMARY The National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) is a national effort to accelerate the understanding of the molecular basis of cancer through the application of large-scale proteome and genome analysis, or proteogenomics. Launched in 2011, CPTAC pioneered the integrated proteogenomic analysis of colorectal, breast and ovarian cancer to reveal new insights into these cancer types, such as identification of proteomic-centric subtypes, prioritization of driver mutations by correlative analysis of copy number alterations and protein abundance, and understanding cancer-relevant pathways through post- translational modifications. In this project, CPTAC will collaborate with the NIH Common Fund Gabriella Miller Kids First Pediatric Research Program (Kids First) to comprehensively characterize pediatric leukemia samples (such as T-cell acute lymphoblastic leukemia, T-ALL, and acute myeloid leukemia, AML) using mass spectrometry-based proteomics. This project will fully integrate proteogenomic information of such leukemia samples to capture and replicate specific cancer phenotype, better understand the interconnection of cancer pathways, identify novel protein targets for targeted therapies and immunotherapies, and to stimulate future pediatric cancer research and precision oncology. The PNNL PCC will perform comprehensive, integrated global proteome and phosphoproteome analyses of a total of 272 pediatric leukemia samples provided by the Kids First collaborators in various forms (such as cell pellets and surfaceome samples), using state-of-the-art liquid chromatography-tandem mass spectrometry instrumentation, highly multiplexed isobaric mass-tag labeling (TMT 18-plex), and integrated sample workflows. The resulting molecular data will become a community resource available at CAVATICA.