Multi-layered proteomics for the characterization of cancer mutations
Genomic mutations are associated with a variety of human diseases but their effect on cellular networks remain incompletely understood. A recent “Nature Communications” paper by the Aebersold group shows how cancer-associated genomic mutations modulate the cellular proteome and are translated into molecular phenotypes.
Large-scale sequencing technologies enabled the comprehensive analysis of genomes and the identification of disease-associated genomic mutations. However, only limited progress has been achieved in systematically mapping the functional repercussions of specific mutations. In this study the authors combined a suite of mass-spectrometry based proteomic techniques to decode the molecular response of cells to genomic lesions. Using this workflow it was determined how the expression of disease-associated mutations in the Dyrk2 kinase alter the composition, topology and activity of this kinase complex. The data showed that cancer point mutations generate mutant-specific proteomic signatures indicating the complexities of the cellular response to perturbations. Further, they found that altered protein-protein interactions caused by the mutations are associated with topological changes and affected phosphorylation of known cancer driver proteins. This work illustrates that the combination of different layers of proteomic information can serve as powerful tool to study the functional consequences of genomic mutations on a broad scale and provides causal links to observed cancer phenotypes.
Link to the paper in external page "Nature Communications"