Advertisement

Topics

DNA methylation, isocitrate dehydrogenase mutation, and survival in glioma.

Summary of "DNA methylation, isocitrate dehydrogenase mutation, and survival in glioma."

Background Although much is known about molecular and chromosomal characteristics that distinguish glioma histological subtypes, DNA methylation patterns of gliomas and their association with other tumor features such as mutation of isocitrate dehydrogenase (IDH) genes have only recently begun to be investigated. Methods DNA methylation of glioblastomas, astrocytomas, oligodendrogliomas, oligoastrocytomas, ependymomas, and pilocytic astrocytomas (n = 131) from the Brain Tumor Research Center at the University of California San Francisco, as well as nontumor brain tissues (n = 7), was assessed with the Illumina GoldenGate methylation array. Methylation data were subjected to recursively partitioned mixture modeling (RPMM) to derive methylation classes. Differential DNA methylation between tumor and nontumor was also assessed. The association between methylation class and IDH mutation (IDH1 and IDH2) was tested using univariate and multivariable analysis for tumors (n = 95) with available substrate for sequencing. Survival of glioma patients carrying mutant IDH (n = 57) was compared with patients carrying wild-type IDH (n = 38) using a multivariable Cox proportional hazards model and Kaplan-Meier analysis. All statistical tests were two-sided. Results We observed a statistically significant association between RPMM methylation class and glioma histological subtype (P < 2.2 × 10(-16)). Compared with nontumor brain tissues, across glioma tumor histological subtypes, the differential methylation ratios of CpG loci were statistically significantly different (permutation P < .0001). Methylation class was strongly associated with IDH mutation in gliomas (P = 3.0 × 10(-16)). Compared with glioma patients whose tumors harbored wild-type IDH, patients whose tumors harbored mutant IDH showed statistically significantly improved survival (hazard ratio of death = 0.27, 95% confidence interval = 0.10 to 0.72). Conclusion The homogeneity of methylation classes for gliomas with IDH mutation, despite their histological diversity, suggests that IDH mutation is associated with a distinct DNA methylation phenotype and an altered metabolic profile in glioma.

Affiliation

Department of Neurological Surgery, Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA 91458. john.wiencke@ucsf.edu.

Journal Details

This article was published in the following journal.

Name: Journal of the National Cancer Institute
ISSN: 1460-2105
Pages: 143-53

Links

DeepDyve research library

PubMed Articles [10657 Associated PubMed Articles listed on BioPortfolio]

Prognostic Molecular and Imaging Biomarkers in Primary Glioblastoma.

Several molecular glioma markers (including isocitrate dehydrogenase 1 [IDH1] mutation, amplification of the epidermal growth factor receptor [EGFR], and methylation of the O6-methylguanine-DNA methyl...

K27M-mutant histone-3 as a novel target for glioma immunotherapy.

Mutation-specific vaccines have become increasingly important in glioma immunotherapy; however, shared neoepitopes are rare. For diffuse gliomas, a driver mutation in the gene for isocitrate dehydroge...

Expression and prognostic value of microRNAs in lower-grade glioma depends on IDH1/2 status.

Histological and genomic characteristics are widely used in glioma management and research. This study investigated their relationship to the expression and prognostic value of microRNAs (miRNAs) in l...

IDH1 Mutation Is an Independent Inferior Prognostic Indicator for Patients with Myelodysplastic Syndromes.

Genomic sequencing technologies have identified isocitrate dehydrogenase (IDH) mutations in haematological malignancies. The prognostic implications of somatic IDH mutation (mIDH) in myelodysplastic s...

Cancer-Associated IDH1 Promotes Growth and Resistance to Targeted Therapies in the Absence of Mutation.

Oncogenic mutations in two isocitrate dehydrogenase (IDH)-encoding genes (IDH1 and IDH2) have been identified in acute myelogenous leukemia, low-grade glioma, and secondary glioblastoma (GBM). Our in...

Clinical Trials [3242 Associated Clinical Trials listed on BioPortfolio]

Noninvasively Predicting Gene Status of Glioma

Malignant gliomas are the most common and deadly primary brain tumors in adults. The clinical outcome of patients with glioblastoma depends on key molecular genetic alteration. Specificall...

An Efficacy and Safety Study of AG-221 (CC-90007) Versus Conventional Care Regimens in Older Subjects With Late Stage Acute Myeloid Leukemia Harboring an Isocitrate Dehydrogenase 2 Mutation

This is an international, multicenter, open-label, randomized, Phase 3 study comparing the efficacy and safety of AG-221 versus conventional care regimens (CCRs) in subjects 60 years or ol...

An Efficacy and Safety Study of AG-221 (CC-90007) Versus Conventional Care Regimens in Older Subjects With Late Stage Acute Myeloid Leukemia Harboring an Isocitrate Dehydrogenase 2 Mutation

This is an international, multicenter, open-label, randomized, Phase 3 study comparing the efficacy and safety of AG-221 versus conventional care regimens (CCRs) in subjects 60 years or ol...

Metformin And Chloroquine in IDH1/2-mutated Solid Tumors

This phase Ib, open-label, single-center, non-randomized clinical trial will evaluate the toxicity and efficacy of metformin and chloroquine in isocitrate dehydrogenase 1/2-mutated (IDH1/2...

A Safety and Efficacy Study of Oral AG-120 Plus Subcutaneous Azacitidine and Oral A-221 Plus Subcutaneous Azacitidine in Subjects With Newly Diagnosed Acute Myeloid Leukemia (AML)

This Phase 1b/2 study is an open-label, randomized, multicenter trial to evaluate the safety and efficacy of oral AG-120 + SC azacitidine and oral A-221 + Subcutaneous (SC) azacitidine in ...

Medical and Biotech [MESH] Definitions

An enzyme of the oxidoreductase class that catalyzes the conversion of isocitrate and NAD+ to yield 2-ketoglutarate, carbon dioxide, and NADH. It occurs in cell mitochondria. The enzyme requires Mg2+, Mn2+; it is activated by ADP, citrate, and Ca2+, and inhibited by NADH, NADPH, and ATP. The reaction is the key rate-limiting step of the citric acid (tricarboxylic) cycle. (From Dorland, 27th ed) (The NADP+ enzyme is EC 1.1.1.42.) EC 1.1.1.41.

A key enzyme in the glyoxylate cycle. It catalyzes the conversion of isocitrate to succinate and glyoxylate. EC 4.1.3.1.

The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.

Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)

Continuance of life or existence especially under adverse conditions; includes methods and philosophy of survival.

Quick Search
Advertisement
 


DeepDyve research library

Relevant Topics

DNA sequencing
DNA sequencing is the process of determining the precise order of nucleotides within a DNA molecule. During DNA sequencing, the bases of a small fragment of DNA are sequentially identified from signals emitted as each fragment is re-synthesized from a ...

Bioinformatics
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

Alzheimer's Disease
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase  'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...


Searches Linking to this Article