Epigenetic modification of DNA by cytosine methylation to produce 5-methylcytosine (5mC) has become well-recognized as an important epigenetic process in human health and disease. Recently, further modification of 5mC by the ten eleven translocated (TET) family of enzymes to produce 5-hydroxymethylcytosine (5hmC) has been described. Brent Orr and Charles Eberhart, together with collaborators in the Cancer Center, used immunohistochemistry to evaluate the distribution of 5hmC in human brain during different periods of development and in a large series of 225 gliomas. They found that during development, 5hmC levels are high in more differentiated compartments like the fetal cortex, but low in the periventricular progenitor cell regions. In brain tumors, 5hmC levels were high in low grade tumors and reduced in malignant glioma. Additionally, they identified a significant relationship between low levels of 5hmC and reduced survival in malignant glioma. This observation was further supported by in silico analysis showing differential expression of genes involved in 5hmC homeostasis in aggressive subsets of glioblastoma. Finally, they found that several genes involved in regulating the levels of 5hmC are also prognostic in malignant glioma. These findings suggest that 5hmC regulation in malignant glioma may represent an important determinant of tumor differentiation and aggressive behavior, as well as a potential therapeutic target. The study was published in PLoS One (http://www.ncbi.nlm.nih.gov/pubmed/22829908).