Proteogenomic Approaches for Childhood Cancer Target Discovery

Background

Childhood solid tumors are characterized by the paucity of coding gene mutations. Due to the availability of whole genome DNA sequencing, wide-ranging discovery of cancer-causing mutations have been enabled across the majority of childhood cancers. However, the pathogenic mechanisms and their therapeutic immune targeting have been difficult to pinpoint, in part due to our limited ability to decipher their functional consequences in cells. Recently developed high-accuracy mass spectrometry proteomics methods can now produce near-comprehensive genome-scale maps of cellular proteomes.

Project Goal

Nathaniel will be working to integrate whole-genome DNA sequencing analysis with no comprehensive proteomics, in order to enable the discovery of neomorphic protein isoforms ad neo-antigens. They will focus on rhabdoid tumors and other refractory childhood solid tumors, which have recently been found to harbor cryptic genomic rearrangements that can produce neomorphic proteins. Essential to this work is a new integrated method for proteogenomic analysis that will be publicly available and used for neo-antigen discovery in rhabdoid and other refractory childhood solid tumors.