As the director of the Center of Epigenetics in the Institute of Basic Biomedical Sciences at the Johns Hopkins University, Andrew Feinberg, MD, expertly explored the epigenetic basis of common human disease during yesterday’s plenary session. Epigenetics encompasses “modifications of DNA or associated factors, that have information content and are maintained during cell division, other than the primary DNA sequence,” Feinberg said. Notably, alterations such as histone modifications and DNA hypo- and hypermethylation have been implicated in several human disease states. Feinberg deftly discussed the importance of such epigenetic variations in the context not only of cancer, but also stem cell reprogramming and autoimmune diseases such as rheumatoid arthritis.

Feinberg also highlighted approaches used by his group to “integrate environmental exposure and DNA variation into modifying the epigenetic genome.”  His plenary detailed not only the current landscape of what we know about epigenetics in the context of human disease, but also its role in the future of healthcare and potentially laboratory medicine.

One major focus of the lecture was the contribution of DNA methylation, which is defined as the covalent addition of a methyl group to a cytosine nucleotide, in cancer. Feinberg explained that regions rich with methylated dinucleotides, referred to as CpG islands, have long been an area of interest for researchers assessing the role of DNA methylation in cancer. “Many of the changes in methylation actually occur adjacent to these CpG islands, in regions referred to as CpG shores,” Fienberg noted.

A surprising recent discovery Fienberg discussed is that large regions of the genome are both hypomethylated and variable in terms of methylation and expression in cancer, as well as in tissue exposed to carcinogenic agents such as sunlight. 

In addition to discussing the role of epigenetic changes in human disease, Feinberg highlighted technologies currently employed to identify regions of DNA methylation. These include array-based approaches developed several years ago that gave us the first comprehensive genome-scale insight into methylation changes in disease development. More recently, his group has worked on new analytical tools applied to whole genome bisulfite sequencing data, revealing changes in both methylation levels and methylation entropy.

Feinberg’s survey of the current state of epigenetics was enlightening. Not only did he convey the critical role of epigenetic alterations in human disease, his plenary also presented attendees with important questions to consider, particularly in the field of precision medicine.  “Precision medicine is not purely genetic; considerations should be made for epigenetics, tissue specificity, and environmental factors,” he said.

While clinical laboratorians are currently focused on the acquisition of genetic information that is either inherited or acquired, Feinberg advised us to consider what lies beyond the genome: the epigenetic changes and post-translational modifications that can impact gene expression and regulation. The buzzword of epigenetics often is casually mentioned when discussing genetic variability, but Feinberg’s plenary provided both a concrete point of view and a look to the future, focused on a more integrated and comprehensive approach to targeted and personalized healthcare.