DNA Methylation Signatures for 2016 WHO Classification Subtypes of Diffuse Gliomas

Overview

Journal Clin Epigenetics

Publisher Biomed Central

Specialty Genetics

Date 2017 Apr 11

PMID 28392842

Citations 12

Authors

Yashna Paul

Baisakhi Mondal

Vikas Patil

Kumaravel Somasundaram

Affiliations

Soon will be listed here.

Abstract

Background: Glioma is the most common of all primary brain tumors with poor prognosis and high mortality. The 2016 World Health Organization classification of the tumors of central nervous system uses molecular parameters in addition to histology to redefine many tumor entities. The new classification scheme divides diffuse gliomas into low-grade glioma (LGG) and glioblastoma (GBM) as per histology. LGGs are further divided into isocitrate dehydrogenase (IDH) wild type or mutant, which is further classified into either oligodendroglioma that harbors 1p/19q codeletion or diffuse astrocytoma that has an intact 1p/19q loci but enriched for ATRX loss and TP53 mutation. GBMs are divided into IDH wild type that corresponds to primary or de novo GBMs and IDH mutant that corresponds to secondary or progressive GBMs. To make the 2016 WHO subtypes of diffuse gliomas more robust, we carried out Prediction Analysis of Microarrays (PAM) to develop DNA methylation signatures for these subtypes.

Results: In this study, we applied PAM on a training set of diffuse gliomas derived from The Cancer Genome Atlas (TCGA) and identified DNA methylation signatures to classify LGG IDH wild type from LGG IDH mutant, LGG IDH mutant with 1p/19q codeletion from LGG IDH mutant with intact 1p/19q loci and GBM IDH wild type from GBM IDH mutant with an accuracy of 99-100%. The signatures were validated using the test set of diffuse glioma samples derived from TCGA with an accuracy of 96 to 99%. In addition, we also carried out additional validation of all three signatures using independent LGG and GBM cohorts. Further, the methylation signatures identified a fraction of samples as discordant, which were found to have molecular and clinical features typical of the subtype as identified by methylation signatures.

Conclusions: Thus, we identified methylation signatures that classified different subtypes of diffuse glioma accurately and propose that these signatures could complement 2016 WHO classification scheme of diffuse glioma.

Citing Articles

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Evaluation of DNA Methylation Array for Glioma Tumor Profiling and Description of a Novel Epi-Signature to Distinguish IDH1/IDH2 Mutant and Wild-Type Tumors.

Schenkel L, Mathew J, Hirte H, Provias J, Pare G, Chong M Genes (Basel). 2022; 13(11).

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Current Opinion on Molecular Characterization for GBM Classification in Guiding Clinical Diagnosis, Prognosis, and Therapy.

Zhang P, Xia Q, Liu L, Li S, Dong L Front Mol Biosci. 2020; 7:562798.

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Beyond IDH-Mutation: Emerging Molecular Diagnostic and Prognostic Features in Adult Diffuse Gliomas.

Mirchia K, Richardson T Cancers (Basel). 2020; 12(7).

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Identification of Prognostic Signatures of Alternative Splicing in Glioma.

Zeng Y, Zhang P, Wang X, Wang K, Zhou M, Long H J Mol Neurosci. 2020; 70(10):1484-1492.

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