Low values of 5-hydroxymethylcytosine (5hmC), the "sixth base," are associated with anaplasia in human brain tumors
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Low values of 5-hydroxymethylcytosine (5hmC), the "sixth base," are associated with anaplasia in human brain tumors. / Kraus, Theo F J; Globisch, Daniel; Wagner, Mirko; Eigenbrod, Sabina; Widmann, David; Münzel, Martin; Müller, Markus; Pfaffeneder, Toni; Hackner, Benjamin; Feiden, Wolfgang; Schüller, Ulrich; Carell, Thomas; Kretzschmar, Hans A.
In: INT J CANCER, Vol. 131, No. 7, 01.10.2012, p. 1577-90.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Low values of 5-hydroxymethylcytosine (5hmC), the "sixth base," are associated with anaplasia in human brain tumors
AU - Kraus, Theo F J
AU - Globisch, Daniel
AU - Wagner, Mirko
AU - Eigenbrod, Sabina
AU - Widmann, David
AU - Münzel, Martin
AU - Müller, Markus
AU - Pfaffeneder, Toni
AU - Hackner, Benjamin
AU - Feiden, Wolfgang
AU - Schüller, Ulrich
AU - Carell, Thomas
AU - Kretzschmar, Hans A
N1 - Copyright © 2012 UICC.
PY - 2012/10/1
Y1 - 2012/10/1
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Anaplasia
KW - Astrocytoma
KW - Brain
KW - Brain Neoplasms
KW - Cerebral Cortex
KW - Child
KW - Child, Preschool
KW - Cytosine
KW - DNA
KW - Epigenesis, Genetic
KW - Female
KW - Humans
KW - Isocitrate Dehydrogenase
KW - Male
KW - Middle Aged
KW - Mutation
KW - Young Adult
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1002/ijc.27429
DO - 10.1002/ijc.27429
M3 - SCORING: Journal article
C2 - 22234893
VL - 131
SP - 1577
EP - 1590
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 7
ER -