Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma
- PMID: 25008768
- DOI: 10.1007/s00401-014-1315-x
Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma
Abstract
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 %). CIMP(pos) (IDH mutant) tumors showed a further separation based on copy-number status of chromosome arms 1p and 19q. CIMP(neg) (IDH wild type) tumors showed hallmark copy-number alterations of glioblastomas, and clustered together with CIMP(neg) 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 CIMP(pos) tumors with 1p/19q codeletion (CIMP-codel) had the best prognosis, followed by patients with CIMP(pos) tumors but intact 1p/19q status (CIMP-non-codel). Patients with CIMP(neg) 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.
Similar articles
-
Assessing CpG island methylator phenotype, 1p/19q codeletion, and MGMT promoter methylation from epigenome-wide data in the biomarker cohort of the NOA-04 trial.Neuro Oncol. 2014 Dec;16(12):1630-8. doi: 10.1093/neuonc/nou138. Epub 2014 Jul 15. Neuro Oncol. 2014. PMID: 25028501 Free PMC article.
-
Clinical insights gained by refining the 2016 WHO classification of diffuse gliomas with: EGFR amplification, TERT mutations, PTEN deletion and MGMT methylation.BMC Cancer. 2019 Oct 17;19(1):968. doi: 10.1186/s12885-019-6177-0. BMC Cancer. 2019. PMID: 31623593 Free PMC article.
-
Impact of gross total resection in patients with WHO grade III glioma harboring the IDH 1/2 mutation without the 1p/19q co-deletion.J Neurooncol. 2016 Sep;129(3):505-514. doi: 10.1007/s11060-016-2201-2. Epub 2016 Jul 11. J Neurooncol. 2016. PMID: 27401154
-
Clinical Relevance of Prognostic and Predictive Molecular Markers in Gliomas.Adv Tech Stand Neurosurg. 2016;(43):91-108. doi: 10.1007/978-3-319-21359-0_4. Adv Tech Stand Neurosurg. 2016. PMID: 26508407 Review.
-
Treatment of anaplastic glioma.Cancer Treat Res. 2015;163:89-101. doi: 10.1007/978-3-319-12048-5_6. Cancer Treat Res. 2015. PMID: 25468227 Review.
Cited by
-
Genetic and epigenetic instability as an underlying driver of progression and aggressive behavior in IDH-mutant astrocytoma.Acta Neuropathol. 2024 Jul 16;148(1):5. doi: 10.1007/s00401-024-02761-7. Acta Neuropathol. 2024. PMID: 39012509 Free PMC article. Review.
-
'The Reports of My Death Are Greatly Exaggerated'-Evaluating the Effect of Necrosis on MGMT Promoter Methylation Testing in High-Grade Glioma.Cancers (Basel). 2024 May 16;16(10):1906. doi: 10.3390/cancers16101906. Cancers (Basel). 2024. PMID: 38791984 Free PMC article.
-
Systemic and local immunosuppression in glioblastoma and its prognostic significance.Front Immunol. 2024 Feb 28;15:1326753. doi: 10.3389/fimmu.2024.1326753. eCollection 2024. Front Immunol. 2024. PMID: 38481999 Free PMC article. Review.
-
General Clinico-Pathological Characteristics in Glioblastomas in Correlation with p53 and Ki67.Medicina (Kaunas). 2023 Oct 30;59(11):1918. doi: 10.3390/medicina59111918. Medicina (Kaunas). 2023. PMID: 38003967 Free PMC article.
-
Tyrosine metabolic reprogramming coordinated with the tricarboxylic acid cycle to drive glioma immune evasion by regulating PD-L1 expression.Ibrain. 2023 May 22;9(2):133-147. doi: 10.1002/ibra.12107. eCollection 2023 Summer. Ibrain. 2023. PMID: 37786553 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials