Intratumoral homogeneity of MGMT promoter hypermethylation as demonstrated in serial stereotactic specimens from anaplastic astrocytomas and glioblastomas.
作者： Eva M. Grasbon-Frodl , Friedrich Wilhelm Kreth , Michael Ruiter , Oliver Schnell , Karl Bise
DOI: 10.1002/IJC.23020
关键词: DNA methylation 、 Biopsy 、 Pathology 、 Tumor progression 、 Anaplastic astrocytoma 、 Biology 、 Methyltransferase 、 Methylation 、 DNA methyltransferase 、 Astrocytoma
摘要: Hypermethylation of the DNA repair gene O6-methyl-guanine methyltransferase (MGMT) has been linked to prolonged survival in glioblastoma patients treated with alkylating agents. It was aimed analyze prospectively whether MGMT status malignant gliomas could be determined from small-sized stereotactic biopsies (maximum volume: 1 mm3). Special attention directed towards intratumoral distribution promoter methylation, protein expression and potential correlations between both. Twenty-five adult were included (20 primary World Health Organisation (WHO) Grade III or IV gliomas, 5 secondary gliomas). About 2–4 biopsy specimens per tumor collected different sites within tumor. Promoter methylation assessed by methylation-specific PCR (MSP) sodium bisulfite sequencing each (overall number specimens: 69). Both methods validated for application tissue samples (1 The analyzed immunohistochemistry. overall rate 30% de novo group 80% progression group. success rates MSP 100% 80%, respectively. Sequence analysis exhibited concordant findings. No differences detected individual 24 25 patients. One false negative result obtained due contamination specimen necrotic tissue. Tissue taken (13 tumors investigated) equal highly similar expression. correlation observed. can reliably biopsies. profile, as defined sequencing, constitutes a homogeneous marker throughout gliomas. lack needs further evaluation. © 2007 Wiley-Liss, Inc.
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