decreased 5-hydroxymethylcytosine is associated with neural progenitor phenotype in normal brain and shorter survival in malignant glioma减少5-hydroxymethylcytosine与神经祖表型正常的大脑和更短的生存恶性神经胶质瘤.pdfVIP

Decreased 5-Hydroxymethylcytosine Is Associated with Neural Progenitor Phenotype in Normal Brain and Shorter Survival in Malignant Glioma 1 4 1,4,5 4 Brent A. Orr *, Michael C. Haffner , William G. Nelson , Srinivasan Yegnasubramanian *, Charles G. Eberhart1,2,3 1 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 2 Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 3 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 4 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, United States of America, 5 Brady Urological Institute, Johns Hopkins University, Baltimore, Maryland, United States of America Abstract 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. In the present study, we used immunohistochemistry to evaluate the distribution of 5hmC in human brain during different periods of development and in a large series of gliomas (n = 225). We 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 adults, we found 5hmC levels to be highest in the cortex, but present in all intrinsic cell types in the brain including stromal elements. In brai