Disambiguating epigenetics

Abstract

An understanding of epigenetics is now essential for the clinical pathologist in terms of disease pathogenesis, prognostication and therapeutic opportunities. Yet epigenetics, the study of inherited altered gene expression despite an unchanged DNA sequence, remains a source of confusion for many. For example, it is often difficult to appreciate parent-of-origin effects involving genomic imprinting including covalent (DNA methylation) and non-covalent changes (DNA-protein and DNA-RNA interactions, chromatin remodelling). In this talk I will highlight the importance of developments in RNA biology with a special focus on non-coding RNAs and microRNAs. Burgeoning subsets of RNA molecules are being identified that do not encode protein and function predominately as regulators of gene expression.¹ One of the most widely studied subset contains microRNAs, which are tiny endogenously-expressed molecules that fine-tune gene expression through several different mechanisms.² In the case of haematological malignancies, profiling of microRNA expression has been shown to correlate with cytogenetic changes, somatic mutations and clinical outcomes in acute myeloid leukaemia, chronic myeloid leukaemia, chronic lymphocytic leukaemia and lymphoma.