Advanced Proteogenomic Analysis Reveals Multiple Peptide Mutations and Complex Immunoglobulin Peptides in Colon Cancer

Aiming toward an improved understanding of the regulation of proteins in cancer, recent studies from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) have focused on analyzing cancer tissue using proteomic technologies and workflows. Although many proteogenomics approaches for the study of cancer samples have been proposed, serious methodological challenges remain, especially in the identification of multiple mutational variants or structural variations such as fusion gene events. In addition, although immune system genes play an important role in cancer, identification of IgG peptides remains challenging in proteomic data sets. Here, we describe an integrative proteogenomic method that extends the limit of proteogenomic searches to identify multiple variant peptides as well as immunoglobulin gene variations/rearrangements using customized mining of RNA-seq data. Our results also provide the first extensive characterization of tumor immune response and demonstrate the potential of this method to improve the molecular characterization of tumor subtypes.