Multiple Myeloma (MM) is an incurable plasma cell neoplasm with a median survival of 3 years. A critical step towards the development of more effective therapies is the identification of dominantly acting oncogenes. We have implemented an integrated oncogenomic approach that utilizes high-resolution gene-specific array-CGH and comprehensive expression profiling to identify the spectrum of genetic alterations in a large panel of MM cell lines (n=46) and annotated primary tumors (n=65). These efforts have uncovered a strikingly high number of novel recurrent focal amplifications and deletions. To select the most critical amplicons, a stringent filtering algorithm that takes in account the amplification level, recurrence and the presence of similar lesions in an extensive array-CGH database of more than 600 tumors and cell lines from different cancer types yielded 13 highly-selected amplicons. Within these, 117 genes demonstrated significant upregulation when compared with normal plasma cells, with 28 genes considered potential targets for Monoclonal Antibodies based on their structural features. This dataset will be prioritized by key parameters including oncogenic validation assays and in vivo testing. The ultimate goal of this proposal is to provide a list of functionally validated antibody targets, which can be enlisted into therapeutic monoclonal antibody development.
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