Proteomic approaches for cancer epigenetics research

ABSTRACT

Introduction: Epigenetic dysregulation drives or supports numerous human cancers. The chromatin landscape in cancer cells is often marked by abnormal histone post-translational modification (PTM) patterns and by aberrant assembly and recruitment of protein complexes to specific genomic loci. Mass spectrometry-based proteomic analyses can support the discovery and characterization of both phenomena.

Areas covered: We broadly divide this literature into two parts: ‘modification-centric’ analyses that link histone PTMs to cancer biology; and ‘complex-centric’ analyses that examine protein–protein interactions that occur de novo as a result of oncogenic mutations. We also discuss proteomic studies of oncohistones. We highlight relevant examples, discuss limitations, and speculate about forthcoming innovations regarding each application.

Expert commentary: ‘Modification-centric’ analyses have been used to further understanding of cancer’s histone code and to identify associated therapeutic vulnerabilities. ‘Complex-centric’ analyses have likewise revealed insights into mechanisms of oncogenesis and suggested potential therapeutic targets, particularly in MLL-associated leukemia. Proteomic experiments have also supported some of the pioneering studies of oncohistone-mediated tumorigenesis. Additional applications of proteomics that may benefit cancer epigenetics research include middle-down and top-down histone PTM analysis, chromatin reader profiling, and genomic locus-specific protein identification. In the coming years, proteomic approaches will remain powerful ways to interrogate the biology of cancer.

KEYWORDS:

• Affinity proteomics
• cancer
• chromatin
• epigenetics
• histones
• readers
• middle-down
• top-down

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

D. Marchione has received funding from the US National Institutes of Health: [NIH TL1TR001880] and [NIH T32GM008275]. J. Wojcik has received funding from the University of Pennsylvania Abramson Cancer Center Paul Calabresi K12 Career Development Award for Clinical Oncology [5K12CA076931]. B.A. Garcia has received funding from the US National Institutes of Health: [NIH GM110174], [NIH CA196539]; and a Robert Arceci Scholar Award from the Leukemia and Lymphoma Society.