Michigan Center for Translational Cancer Proteogenomics

Abstract Pediatric cancers exhibit unique biological features, including significant germline predisposition and aberrant developmental pathway activation, necessitating specialized research approaches. This supplement proposes to expand the University of Michigan Proteogenomic Data Analysis Center (PGDAC) to perform comprehensive proteogenomic analyses tailored for the Gabriella Miller Kids First (Kids First) cohort and other pediatric datasets. We will create 'ProKids', an integrated, harmonized pediatric proteogenomic resource (focusing initially on hematological malignancies), enabling comparative analyses across diverse pediatric malignancies and against adult cancers to identify unique molecular features and signaling alterations. Key objectives include: 1) Utilizing 'ProKids' for multi-omic comparative analyses to discover novel therapeutic targets, with a specific focus on identifying cell surface antigens for immunotherapies; 2) Integrating proteogenomic data with germline sequencing to functionally interpret inherited variants (including VUS) and understand their impact on pediatric cancer biology and outcomes; and 3) Interrogating tumor proteomes, PTMs for aberrant developmental signatures to uncover unique dependencies and vulnerabilities suitable for targeted therapies. This initiative will leverage proteogenomics to unlock unprecedented insights into pediatric cancers, providing critical resources and knowledge to advance treatments for childhood illnesses.