Low values of 5-hydroxymethylcytosine (5hmC), the "sixth base," are associated with anaplasia in human brain tumors.

Abstract

5-Methylcytosine (5 mC) in genomic DNA has important epigenetic functions in embryonic development and tumor biology. 5-Hydroxymethylcytosine (5 hmC) is generated from 5 mC by the action of the TET (Ten-Eleven-Translocation) enzymes and may be an intermediate to further oxidation and finally demethylation of 5 mC. We have used immunohistochemistry (IHC) and isotope-based liquid chromatography mass spectrometry (LC-MS) to investigate the presence and distribution of 5 hmC in human brain and brain tumors. In the normal adult brain, IHC identified 61.5% 5 hmC positive cells in the cortex and 32.4% 5 hmC in white matter (WM) areas. In tumors, positive staining of cells ranged from 1.1% in glioblastomas (GBMs) (WHO Grade IV) to 8.9% in Grade I gliomas (pilocytic astrocytomas). In the normal adult human brain, LC-MS also showed highest values in cortical areas (1.17% 5 hmC/dG [deoxyguanosine]), in the cerebral WM we measured around 0.70% 5 hmC/dG. levels were related to tumor differentiation, ranging from lowest values of 0.078% 5 hmC/dG in GBMs (WHO Grade IV) to 0.24% 5 hmC/dG in WHO Grade II diffuse astrocytomas. 5 hmC measurements were unrelated to 5 mC values. We find that the number of 5 hmC positive cells and the amount of 5 hmC/dG in the genome that has been proposed to be related to pluripotency and lineage commitment in embryonic stem cells is also associated with brain tumor differentiation and anaplasia.

• Authors: Theo F J Kraus, Daniel Globisch, Mirko Wagner, Sabina Eigenbrod, David Widmann, Martin Münzel, Markus Müller, Toni Pfaffeneder, Benjamin Hackner, Wolfgang Feiden, Ulrich Schüller, Thomas Carell, Hans A Kretzschmar
• Journal: International journal of cancer (Int J Cancer) Vol. 131 Issue 7 Pg. 1577-90 (Oct 01 2012) ISSN: 1097-0215 [Electronic] United States
• PMID: 22234893 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 UICC.

Chemical References

• 5-hydroxymethylcytosine
• 5-Methylcytosine
• Cytosine
• DNA
• Isocitrate Dehydrogenase
• IDH1 protein, human

Topics

• 5-Methylcytosine (analogs & derivatives)
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anaplasia
• Astrocytoma (genetics)
• Brain (metabolism)
• Brain Neoplasms (genetics, pathology)
• Cerebral Cortex (metabolism)
• Child
• Child, Preschool
• Cytosine (analogs & derivatives, analysis)
• DNA (chemistry)
• Epigenesis, Genetic
• Female
• Humans
• Isocitrate Dehydrogenase (genetics)
• Male
• Middle Aged
• Mutation
• Young Adult