The hypermethylation of the O 6 ‐methylguanine‐DNA methyltransferase gene promoter in gliomas—correlation with array comparative genome hybridization results and IDH1 mutation
Abstract The use of molecular markers in the diagnostics of gliomas aids histopathological diagnosis and allows their further classification into clinically significant subgroups. The aim of this study was to characterize the methylation pattern of the O 6 ‐methylguanine‐DNA methyltransferase ( MGMT...
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Published in | Genes chromosomes & cancer Vol. 51; no. 1; pp. 20 - 29 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.01.2012
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Online Access | Get full text |
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Summary: | Abstract
The use of molecular markers in the diagnostics of gliomas aids histopathological diagnosis and allows their further classification into clinically significant subgroups. The aim of this study was to characterize the methylation pattern of the O
6
‐methylguanine‐DNA methyltransferase (
MGMT
) promoter, gene copy number aberrations, and isocitrate dehydrogenase I (IDH1) mutation in gliomas. We studied 51 gliomas (15 oligodendrogliomas, 18 oligoastrocytomas, 3 astrocytomas, and 15 glioblastomas) by pyrosequencing, array comparative genome hybridization (CGH), and immunohistochemistry.
MGMT
hypermethylation was observed in 100% of oligoastrocytomas, 93% of oligodendrogliomas, and 47% of glioblastomas. The most frequently altered chromosomal regions were deletions of 1p31.1/21.1‐22.2 and 19q13.3qter in oligodendroglial tumors, and losses of 9p21.3, 10q25.3qter, and 10q26.13‐26.2 in glioblastomas. Deletions on 9p and 10q, and gain of 7p were associated with the unmethylated
MGMT
phenotype, whereas deletion of 19q and oligodendroglial morphology was associated with
MGMT
hypermethylation.
IDH1
mutation showed positive correlation with
MGMT
hypermethylation and loss of 1p/19q. Our results suggest that
MGMT
promoter methylation, analyzed by pyrosequencing, is a frequent event in oligodendroglial tumors, and it correlates with
IDH1
mutation and 19q loss in gliomas. Pyrosequencing proved a good method for assessing the degree of
MGMT
methylation in formalin‐fixed paraffin‐embedded glioma samples. However, further studies are needed to confirm a clinically relevant cut‐off point for
MGMT
methylation in gliomas. © 2011 Wiley Periodicals, Inc. |
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ISSN: | 1045-2257 1098-2264 |
DOI: | 10.1002/gcc.20927 |