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Title:
Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma | Acta Neuropathologica
Description:
The outcome of patients with anaplastic gliomas varies considerably. Whether a molecular classification of anaplastic gliomas based on large-scale genomic or epigenomic analyses is superior to histopathology for reflecting distinct biological groups, predicting outcomes and guiding therapy decisions has yet to be determined. Epigenome-wide DNA methylation analysis, using a platform which also allows the detection of copy-number aberrations, was performed in a cohort of 228 patients with anaplastic gliomas (astrocytomas, oligoastrocytomas, and oligodendrogliomas), including 115 patients of the NOA-04 trial. We further compared these tumors with a group of 55 glioblastomas. Unsupervised clustering of DNA methylation patterns revealed two main groups correlated with IDH status: CpG island methylator phenotype (CIMP) positive (77.5 %) or negative (22.5 %). CIMPpos (IDH mutant) tumors showed a further separation based on copy-number status of chromosome arms 1p and 19q. CIMPneg (IDH wild type) tumors showed hallmark copy-number alterations of glioblastomas, and clustered together with CIMPneg glioblastomas without forming separate groups based on WHO grade. Notably, there was no molecular evidence for a distinct biological entity representing anaplastic oligoastrocytoma. Tumor classification based on CIMP and 1p/19q status was significantly associated with survival, allowing a better prediction of outcome than the current histopathological classification: patients with CIMPpos tumors with 1p/19q codeletion (CIMP-codel) had the best prognosis, followed by patients with CIMPpos tumors but intact 1p/19q status (CIMP-non-codel). Patients with CIMPneg anaplastic gliomas (GBM-like) had the worst prognosis. Collectively, our data suggest that anaplastic gliomas can be grouped by IDH and 1p/19q status into three molecular groups that show clear links to underlying biology and a significant association with clinical outcome in a prospective trial cohort.
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Keywords {🔍}
pubmed, article, google, scholar, cas, cancer, central, heidelberg, anaplastic, idh, germany, german, gliomas, tumors, research, acta, methylation, wick, molecular, mutations, department, glioma, glioblastoma, neuropathol, center, university, supplementary, material, wiestler, capper, patients, oncol, christian, classification, distinct, trial, dktk, analysis, dna, groups, jones, korshunov, hartmann, genomic, status, tumor, clin, cell, consortium, dkfz,
Topics {✒️}
month download article/chapter van den bent integrated dna methylation copy-number profiling identify andreas von deimling christel herold-mende idh wild type biomarker-based treatment decisions idh-mutated oligodendroglial tumors intact 1p/19q status full article pdf central nervous system integrated genomic analysis related subjects partner site essen/düsseldorf show clear links mgmt promoter methylation privacy choices/manage cookies mgmt methylation analysis dna methylation somatic genomic landscape copy-number aberrations copy-number status verhaak rgw intrinsic molecular subtypes liu x parsons dw brain tumor immunology large-scale genomic genomic culprits emerge driver genomic alterations biologically relevant groups distinct cpg regions german cancer aid german cancer consortium author information authors wolfgang wick tert promoter mutations phase iii trial von deimling andreas unterberg 1p/19q status noa-08 study collective glioma hypermethylator phenotype article wiestler main groups correlated guiding therapy decisions predictive molecular markers chromosome arms 1p current histopathological classification
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headline:Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma
description:
The outcome of patients with anaplastic gliomas varies considerably. Whether a molecular classification of anaplastic gliomas based on large-scale genomic or epigenomic analyses is superior to histopathology for reflecting distinct biological groups, predicting outcomes and guiding therapy decisions has yet to be determined. Epigenome-wide DNA methylation analysis, using a platform which also allows the detection of copy-number aberrations, was performed in a cohort of 228 patients with anaplastic gliomas (astrocytomas, oligoastrocytomas, and oligodendrogliomas), including 115 patients of the NOA-04 trial. We further compared these tumors with a group of 55 glioblastomas. Unsupervised clustering of DNA methylation patterns revealed two main groups correlated with IDH status: CpG island methylator phenotype (CIMP) positive (77.5 %) or negative (22.5 %). CIMPpos (IDH mutant) tumors showed a further separation based on copy-number status of chromosome arms 1p and 19q. CIMPneg (IDH wild type) tumors showed hallmark copy-number alterations of glioblastomas, and clustered together with CIMPneg glioblastomas without forming separate groups based on WHO grade. Notably, there was no molecular evidence for a distinct biological entity representing anaplastic oligoastrocytoma. Tumor classification based on CIMP and 1p/19q status was significantly associated with survival, allowing a better prediction of outcome than the current histopathological classification: patients with CIMPpos tumors with 1p/19q codeletion (CIMP-codel) had the best prognosis, followed by patients with CIMPpos tumors but intact 1p/19q status (CIMP-non-codel). Patients with CIMPneg anaplastic gliomas (GBM-like) had the worst prognosis. Collectively, our data suggest that anaplastic gliomas can be grouped by IDH and 1p/19q status into three molecular groups that show clear links to underlying biology and a significant association with clinical outcome in a prospective trial cohort.
datePublished:2014-07-10T00:00:00Z
dateModified:2014-07-10T00:00:00Z
pageStart:561
pageEnd:571
sameAs:https://doi.org/10.1007/s00401-014-1315-x
keywords:
Anaplastic glioma
IDH
G-CIMP
1p/19q
450 k
Pathology
Neurosciences
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headline:Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma
description:
The outcome of patients with anaplastic gliomas varies considerably. Whether a molecular classification of anaplastic gliomas based on large-scale genomic or epigenomic analyses is superior to histopathology for reflecting distinct biological groups, predicting outcomes and guiding therapy decisions has yet to be determined. Epigenome-wide DNA methylation analysis, using a platform which also allows the detection of copy-number aberrations, was performed in a cohort of 228 patients with anaplastic gliomas (astrocytomas, oligoastrocytomas, and oligodendrogliomas), including 115 patients of the NOA-04 trial. We further compared these tumors with a group of 55 glioblastomas. Unsupervised clustering of DNA methylation patterns revealed two main groups correlated with IDH status: CpG island methylator phenotype (CIMP) positive (77.5 %) or negative (22.5 %). CIMPpos (IDH mutant) tumors showed a further separation based on copy-number status of chromosome arms 1p and 19q. CIMPneg (IDH wild type) tumors showed hallmark copy-number alterations of glioblastomas, and clustered together with CIMPneg glioblastomas without forming separate groups based on WHO grade. Notably, there was no molecular evidence for a distinct biological entity representing anaplastic oligoastrocytoma. Tumor classification based on CIMP and 1p/19q status was significantly associated with survival, allowing a better prediction of outcome than the current histopathological classification: patients with CIMPpos tumors with 1p/19q codeletion (CIMP-codel) had the best prognosis, followed by patients with CIMPpos tumors but intact 1p/19q status (CIMP-non-codel). Patients with CIMPneg anaplastic gliomas (GBM-like) had the worst prognosis. Collectively, our data suggest that anaplastic gliomas can be grouped by IDH and 1p/19q status into three molecular groups that show clear links to underlying biology and a significant association with clinical outcome in a prospective trial cohort.
datePublished:2014-07-10T00:00:00Z
dateModified:2014-07-10T00:00:00Z
pageStart:561
pageEnd:571
sameAs:https://doi.org/10.1007/s00401-014-1315-x
keywords:
Anaplastic glioma
IDH
G-CIMP
1p/19q
450 k
Pathology
Neurosciences
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