scholarly journals Pleomorphic xanthoastrocytoma is a heterogeneous entity with pTERT mutations prognosticating shorter survival

2022 ◽  
Vol 10 (1) ◽  
Author(s):  
Azadeh Ebrahimi ◽  
Andrey Korshunov ◽  
Guido Reifenberger ◽  
David Capper ◽  
Joerg Felsberg ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Pleomorphic Xanthoastrocytoma ◽  
Histopathological Diagnosis ◽  
Lower Grade ◽  
Tumor Type ◽  
Methylation Analysis ◽  
Diagnostic Challenge ◽  
Methylation Array ◽  
Who Grade ◽  
Dna Methylation Analysis

AbstractPleomorphic xanthoastrocytoma (PXA) in its classic manifestation exhibits distinct morphological features and is assigned to CNS WHO grade 2 or grade 3. Distinction from glioblastoma variants and lower grade glial and glioneuronal tumors is a common diagnostic challenge. We compared a morphologically defined set of PXA (histPXA) with an independent set, defined by DNA methylation analysis (mcPXA). HistPXA encompassed 144 tumors all subjected to DNA methylation array analysis. Sixty-two histPXA matched to the methylation class mcPXA. These were combined with the cases that showed the mcPXA signature but had received a histopathological diagnosis other than PXA. This cohort constituted a set of 220 mcPXA. Molecular and clinical parameters were analyzed in these groups. Morphological parameters were analyzed in a subset of tumors with FFPE tissue available. HistPXA revealed considerable heterogeneity in regard to methylation classes, with methylation classes glioblastoma and ganglioglioma being the most frequent mismatches. Similarly, the mcPXA cohort contained tumors of diverse histological diagnoses, with glioblastoma constituting the most frequent mismatch. Subsequent analyses demonstrated the presence of canonical pTERT mutations to be associated with unfavorable prognosis among mcPXA. Based on these data, we consider the tumor type PXA to be histologically more varied than previously assumed. Histological approach to diagnosis will predominantly identify cases with the established archetypical morphology. DNA methylation analysis includes additional tumors in the tumor class PXA that share similar DNA methylation profile but lack the typical morphology of a PXA. DNA methylation analysis also assist in separating other tumor types with morphologic overlap to PXA. Our data suggest the presence of canonical pTERT mutations as a robust indicator for poor prognosis in methylation class PXA.

scholarly journals DNA methylation analysis of benign and atypical meningiomas: correlation between RUNX3 methylation and WHO grade

2015 ◽  
Vol 141 (9) ◽  
pp. 1593-1601 ◽  
Author(s):  
Aleksandra Majchrzak-Celińska ◽  
Jarosław Paluszczak ◽  
Marlena Szalata ◽  
Anna-Maria Barciszewska ◽  
Stanisław Nowak ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methylation Analysis ◽  
Who Grade ◽  
Atypical Meningiomas ◽  
Dna Methylation Analysis

scholarly journals The Prognostic Value of Methylation Signatures and NF2 Mutations in Atypical Meningiomas

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1262
Author(s):  
Rahmina Meta ◽  
Henning B. Boldt ◽  
Bjarne W. Kristensen ◽  
Felix Sahm ◽  
Wenche Sjursen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Prognostic Value ◽  
Methylation Analysis ◽  
Who Grade ◽  
Group I ◽  
Genome Wide ◽  
Atypical Meningiomas ◽  
Dna Methylation Analysis ◽  
Recurrence Group ◽  
Mutation Analyses

Background: Due to the solely subjective histopathological assessment, the WHO 2016 classification of human meningiomas is subject to interobserver variation. Consequently, the need for more reliable and objective markers are highly needed. The aim of this pilot study was to apply genome-wide DNA methylation analysis on a series of atypical meningiomas to evaluate the practical utility of this approach, examine whether prognostic subclasses are achieved and investigate whether there is an association between the methylation subclasses with poor prognosis and time to recurrence. NF1/2 mutation analyses were also performed to explore the prognostic value of such mutations in these atypical meningiomas. Methods: Twenty intracranial WHO grade II atypical meningiomas from adult patients were included. They consisted of 10 cases with recurrence (group I), and 10 cases without recurrence (group II). The formalin-fixed and paraffin-embedded tissues underwent standardized genome-wide DNA methylation analysis, and the profiles were matched with the reference library and tumor classifier from Heidelberg. NF1/2 somatic mutation analyses were performed using the CNSv1panel from Düsseldorf. Results: Eighteen out of 20 cases matched to the meningioma class using the common brain tumor classifier (v11b4). Four of these cases matched to a methylation subclass related to a prognostic subgroup based on a cut-off of 0.9. NF2 mutations were detected in 55% of cases across both groups, and the most prominent copy number alterations were chromosomal losses of 22q, 1p and 14q. No significant NF1 mutations were identified. Conclusions: Genome-wide DNA methylation profiling represents a useful tool in the diagnostics of meningiomas, however, methodological adjustments need to be addressed.

P04.07 The molecular evolution of oligodendrogliomas

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii20-ii20
Author(s):  
M Padovan ◽  
W Vallentgoed ◽  
I de Heer ◽  
G Lombardi ◽  
M van den Bent ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Clinical Data ◽  
De Novo ◽  
Tumour Progression ◽  
Dna Demethylation ◽  
Methylation Analysis ◽  
Who Grade ◽  
Malignancy Grade ◽  
Grade 3 ◽  
Dna Methylation Analysis

Abstract BACKGROUND Oligodendroglioma (OD) is defined by the presence of both IDH1/2 mutation and 1p/19q codeletion. Although prognosis of OD patients is relatively favorable, tumours usually relapse and often evolve to a higher malignancy grade, with some acquiring the treatment induced hypermutated phenotype. To better understand how these tumours evolve in time, we examined the molecular differences between matched primary and recurrent ODs. MATERIAL AND METHODS We identified 21 patients who underwent surgery at least twice [male: 11, female: 10, median age: 44 years (31–66)]. Clinical data were available for 14/21 patients: 5/14 received a treatment between resections [4 radiotherapy, 1 radiotherapy followed by PCV chemotherapy]; median time from the first to the second surgery was 71.5 months (12–158). Whole genome DNA-methylation analysis was performed using Illumina’s MethylationEPIC ‘850K’ BeadChip. Results were evaluated using the Molecularneuropathology.org platform (version 3.1.5) and in R. RESULTS Most samples were WHO grade 2 ODs [14, 10 and 1 tumours in first, second and third resection group, respectively]; WHO grade 3 was found in 6, 10 and 3 tumours in first, second and third resection, respectively; in 4 patients the tumour showed malignant progression from grade 2 to 3. Most ODs exhibited an IDH1 R132H mutation [17/21 patients]; in no cases was IDH1/2 mutation lost during progression. DNA methylation analysis was successfully performed in 41/45 cases [primary OD: 17, recurrent OD: 24] for a total of 18 matched pairs. 37 samples were assigned to the “IDH mutant glioma, subclass 1p/19q codeleted OD”; the remaining 4 were assigned to various other methylation classes but CNV (copy number variation) analysis confirmed the 1p19q codeletion in all samples. Recurrent tumours exhibited de novo loss of chromosome 4 in 3/24 cases (12.5%) and loss of chromosome 13 in 3/24 cases (12.5%). In unsupervised analysis of the 1000 most variable CpG sites, samples from the same patient clustered together. This indicates that the inter-tumour variability is greater than the intra-, temporal- or grading variability between tumours. There were no overt differences in DNA methylation levels between the primary and matched recurrent OD. However, lower genome wide DNA methylation levels were observed in tumours that dedifferentiated to grade 3 ODs compared to those of grade 2, indicating that DNA demethylation is associated to higher malignancy grade. CONCLUSION DNA methylation analysis in a cohort of primary and recurrent oligodendrogliomas highlights the genomic and epi-genetic changes that are acquired at tumour progression. We are currently expanding the cohort and collecting/integrating the clinical data to better explore the evolution of recurrent ODs.

scholarly journals P46.03 DNA Methylation Analysis in Smokers and Non-Smokers (Passive and ex-Smokers)

2021 ◽  
Vol 16 (3) ◽  
pp. S490
Author(s):  
D.M. Aguilar-Beltrán ◽  
A.G. Alcázar-Ramos ◽  
A.L. Vega-Rodríguez ◽  
D.G. García-Gutiérrez ◽  
A.D. Bertadillo-Jilote ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methylation Analysis ◽  
Dna Methylation Analysis

scholarly journals DNA Methylation in Solid Tumors: Functions and Methods of Detection

2021 ◽  
Vol 22 (8) ◽  
pp. 4247
Author(s):  
Andrea Martisova ◽  
Jitka Holcakova ◽  
Nasim Izadi ◽  
Ravery Sebuyoya ◽  
Roman Hrstka ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Solid Tumors ◽  
Epigenetic Modification ◽  
Single Gene ◽  
Restriction Enzymes ◽  
Methylation Analysis ◽  
Cpg Dinucleotides ◽  
Sequencing Technologies ◽  
Genome Level ◽  
Dna Methylation Analysis

DNA methylation, i.e., addition of methyl group to 5′-carbon of cytosine residues in CpG dinucleotides, is an important epigenetic modification regulating gene expression, and thus implied in many cellular processes. Deregulation of DNA methylation is strongly associated with onset of various diseases, including cancer. Here, we review how DNA methylation affects carcinogenesis process and give examples of solid tumors where aberrant DNA methylation is often present. We explain principles of methods developed for DNA methylation analysis at both single gene and whole genome level, based on (i) sodium bisulfite conversion, (ii) methylation-sensitive restriction enzymes, and (iii) interactions of 5-methylcytosine (5mC) with methyl-binding proteins or antibodies against 5mC. In addition to standard methods, we describe recent advances in next generation sequencing technologies applied to DNA methylation analysis, as well as in development of biosensors that represent their cheaper and faster alternatives. Most importantly, we highlight not only advantages, but also disadvantages and challenges of each method.

scholarly journals Ewastools: Infinium Human Methylation BeadChip pipeline for population epigenetics integrated into Galaxy

GigaScience ◽  
2020 ◽  
Vol 9 (5) ◽  
Author(s):  
Katarzyna Murat ◽  
Björn Grüning ◽  
Paulina Wiktoria Poterlowicz ◽  
Gillian Westgate ◽  
Desmond J Tobin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Association Studies ◽  
Methylation Analysis ◽  
Web Based ◽  
Array Platform ◽  
Complex Evaluation ◽  
The Galaxy ◽  
Population Epigenetics ◽  
Analyse Data ◽  
Dna Methylation Analysis

Abstract Background Infinium Human Methylation BeadChip is an array platform for complex evaluation of DNA methylation at an individual CpG locus in the human genome based on Illumina’s bead technology and is one of the most common techniques used in epigenome-wide association studies. Finding associations between epigenetic variation and phenotype is a significant challenge in biomedical research. The newest version, HumanMethylationEPIC, quantifies the DNA methylation level of 850,000 CpG sites, while the previous versions, HumanMethylation450 and HumanMethylation27, measured >450,000 and 27,000 loci, respectively. Although a number of bioinformatics tools have been developed to analyse this assay, they require some programming skills and experience in order to be usable. Results We have developed a pipeline for the Galaxy platform for those without experience aimed at DNA methylation analysis using the Infinium Human Methylation BeadChip. Our tool is integrated into Galaxy (http://galaxyproject.org), a web-based platform. This allows users to analyse data from the Infinium Human Methylation BeadChip in the easiest possible way. Conclusions The pipeline provides a group of integrated analytical methods wrapped into an easy-to-use interface. Our tool is available from the Galaxy ToolShed, GitHub repository, and also as a Docker image. The aim of this project is to make Infinium Human Methylation BeadChip analysis more flexible and accessible to everyone.

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