Functional proteomic biomarkers in cancer

Beyond penetrant germline and somatic mutations, there are substantial challenges in extrapolating phenotypes from linear DNA sequences and transcriptomics. This brings a molecular pathology emphasis to the properties of the main players responsible for executing actions, proteins. The proteomic attribute most frequently determined in pathology is (relative) content, but for many candidate biomarkers this is not the most important feature to understand. In keeping pace with the depth of knowledge of the mechanisms underlying pathologies, we need to ask more sophisticated questions about the state of proteins, for example, their oligomerization status, modification status, and location. This demands hitherto nonroutine approaches to proteomics, which we will discuss in this brief perspective.