Epigenomics-Based Diagnostics

The term “epigenetics,” first coined in 1942, refers to heritable traits of cells (over many rounds of cell division) that do not involve changes to the underlying DNA sequence. The 2 predominant epigenetic mechanisms are DNA methylation and histone modification.Epigenetic changes, especially methylation of DNA at the 5 position of cytosine, which occurs in cytosine/guanine-rich regions (CpG islands), may have major effects on gene transcription. For example, it is known that extensive methylation at GC-rich regions of gene promoters or other areas can dramatically affect gene transcription and consequently the whole biology of a particular cell. Epigenetic changes are preserved when cells divide. Although it is well-known that cancer may be caused by the loss of tumor suppressor genes (e.g., through mutation or deletion), another major mechanism of silencing critical genes is through methylation. There are numerous examples of genes that can be silenced by methylation. It is thus reasonable to suggest that DNA methylation may be a marker of gene silencing and that such modifications may correlate with cancer initiation and progression. For this reason, it is likely that epigenetic changes in DNA may carry diagnostic, prognostic, or predictive information. It is thus not surprising that epigenomic/epigenetic changes have attracted increased attention recently for their possible application in cancer and other disease diagnostics. In this Q&A, 4 experts in the field discuss the present and future of epigenomics as they apply to diagnostic applications.Could you briefly describe the field of epigenomics? David Sidransky2: The field of epigenomics is focused on finding genomic alterations beyond changes in DNA sequence.Peter W. Laird3: Epigenomics is the genome-scale study of the distribution of epigenetic marks, which are stable modifications to DNA or DNA packaging that convey nongenetically encoded heritable information. Although there is some debate as …