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.