Cancer Epigenomics: Proper Controls and the Road to Clinical Translation
This review highlights how NGS-based technologies have revealed that cancer epigenomes are dominated by patterns from the cell-of-origin, meaning tumour-specific epigenetic changes must be carefully redefined against appropriate controls. The authors discuss mechanisms behind cancer-associated alterations in DNA methylation, histone modifications, and chromatin accessibility, including the roles of mutated epigenetic modifiers and oncohistones. Proper control tissue selection emerges as a critical and underappreciated challenge for translational epigenomic biomarker development.
The original study
Epigenetic signatures in cancer: proper controls, current challenges and the potential for clinical translation.
- Authors
- Mancarella D, Plass C
- Journal
- Genome medicine
- Type
- Journal Article, Research Support, Non-U.S. Gov't, Review
- PMID
- 33568205
Original abstract
Epigenetic alterations are associated with normal biological processes such as aging or differentiation. Changes in global epigenetic signatures, together with genetic alterations, are driving events in several diseases including cancer. Comparative studies of cancer and healthy tissues found alterations in patterns of DNA methylation, histone posttranslational modifications, and changes in chromatin accessibility. Driven by sophisticated, next-generation sequencing-based technologies, recent studies discovered cancer epigenomes to be dominated by epigenetic patterns already present in the cell-of-origin, which transformed into a neoplastic cell. Tumor-specific epigenetic changes therefore need to be redefined and factors influencing epigenetic patterns need to be studied to unmask truly disease-specific alterations. The underlying mechanisms inducing cancer-associated epigenetic alterations are poorly understood. Studies of mutated epigenetic modifiers, enzymes that write, read, or edit epigenetic patterns, or mutated chromatin components, for example oncohistones, help to provide functional insights on how cancer epigenomes arise. In this review, we highlight the importance and define challenges of proper control tissues and cell populations to exploit cancer epigenomes. We summarize recent advances describing mechanisms leading to epigenetic changes in tumorigenesis and briefly discuss advances in investigating their translational potential.