Germline-driven replication repair-deficient high-grade gliomas exhibit unique hypomethylation patterns hypomethylation patterns
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA661205 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Replication repair deficiency (RRD) leading to hypermutation is an important driving mechanism of high grade glioma (HGG) occurring predominantly in the context of germline mutations in RRD-associated genes. Although HGG present specific patterns of DNA methylation corresponding to oncogenic mutations, this has not been well studied in replication repair deficient tumors. We analyzed 51 HGG arising in the background of gene mutations in RRD utilizing either 450k or 850k methylation arrays. These were compared with HGG not known to be from patients with RRD. RRD HGG harboring secondary mutations in glioma genes such as IDH1 and H3F3A displayed a methylation pattern corresponding to these methylation subgroups. Strikingly, RRD HGG lacking these known secondary mutations clustered together with an incompletely described group of HGG previously labelled “Wild type-C” or “Paediatric RTK 1”. Independent analysis of two comparator HGG cohorts showed that other RRD/hypermutant tumors clustered within these subgroups suggesting that undiagnosed RRD may be driving some HGG clustering in this location. RRD HGG displayed a unique CpG Island Demethylator Phenotype in contrast to the CpG Island Methylator Phenotype described in other cancers. Hypomethylation was enriched at gene promoters with prominent demethylation in genes and pathways critical to cellular survival including cell cycle, gene expression, cellular metabolism and organization. These data suggest that methylation arrays may provide diagnostic information for the detection of RRD HGG. Furthermore, our findings highlight the unique natural selection pressures in these highly dysregulated, hypermutant cancers and provide novel impact of hypermutation and RRD on the cancer epigenome.
2020-11-02 | GSE157397 | GEO
Project description:We have used Illumina Infinium HumanMethylation450 BeadChip array profiling to profile paediatric high grade gliomas and diffuse intrinsic pontine gliomas. The 450K methylation array is being used to separate brain tumour samples on the basis of their methylation profiles which represent the cell of origin the time and place in which tumours arise. Methylation arrays provide data for an integrated molecular diagnosis of brain tumours and define specific molecular subgroups and subtypes of high grade gliomas carrying distinct driver mutations and patterns of somatic alterations. These data form part of an integrated meta-analysis of high grade gliomas in children combining DNA copy number, methylation and high throughput sequencing datasets.
2017-09-28 | E-MTAB-5528 | biostudies-arrayexpress
Project description:Categorisation of LGGs related to their lesion site (infratentorial vs. supratentorial) 40 Low grade gliomas samples
2013-09-21 | E-GEOD-28238 | biostudies-arrayexpress
Project description:Low grade gliomas subtype analysis
| PRJEB9786 | ENA
Project description:We carried out the analyses of chromosome variations between low-grade and high-grade gliomas in Chinese population. We found out the differences in chromosomes, cytobands, genes, pathways and GO functions. To identify the glioma tissue-specific genomic alterations and compare the genomic variations between low-grade and high-grade gliomas.
2015-01-03 | E-GEOD-34888 | biostudies-arrayexpress
Project description:In this study we performed gene expression profiling of 14 cases of grade II gliomas. The results of these analysis were used in unsupervised analyses to compare correlations between the histological subtype of grade II gliomas and gene expression profiles Total RNA was isolated from 14 tumor tissue of patients, which included 5 astrocytomas WHO grade II (T2), 5 oligodendro-gliomas WHO grade II (T2) and 4 ependymomas WHO grade II (T2) samples, in additional to 4 normal tissues. The genome-wide expression analysis was first performed by directly comparing the expression profile of highly enriched different kinds of grade II gliomas and normal tissues, we then applied various data-mining methods to process the 14 different types of grade II gliomas tissues sample.
2010-12-31 | E-GEOD-21354 | biostudies-arrayexpress
Project description:<p>Pediatric low-grade gliomas (PLGGs) are among the most common solid tumors in children but, apart from mutations or duplications in the BRAF kinase in specific subclasses, few genetic driver events are known. Diffuse PLGGs compose a set of uncommon subtypes that exhibit invasive growth and are therefore especially challenging clinically. These tumors are particularly poorly understood. We performed high-resolution copy-number analysis of 44 diffuse PLGGs to identify recurrent alterations. Diffuse PLGGs exhibited fewer such alterations than adult low-grade gliomas, but we identified several significantly recurrent events. The most significant event, 8q13.1 gains, was observed in 28% of diffuse astrocytoma WHO grade II (DA2) and resulted in partial duplication of the transcription factor MYBL1 with truncation of its C-terminal negative-regulatory domain. A similar recurrent deletion-truncation breakpoint was identified in two angiocentric gliomas in the related gene MYB on 6q23.3. Whole genome sequencing of a MYBL1-rearranged diffuse astrocytoma grade II demonstrated MYBL1 tandem duplication and few other events. Two truncated MYBL1 transcripts identified in this tumor induced anchorage-independent growth when expressed in 3T3 cells and tumor formation in nude mice. Truncated transcripts were also expressed in two additional tumors with MYBL1 partial duplication. Our results define clinically relevant molecular subclasses of diffuse PLGGs and highlight a potential role for the MYB family in the biology of low-grade gliomas. "Reprinted from www.pnas.org/cgi/doi/10.1073/pnas.1300252110 with permission from PNAS." </p>
| phs000614 | dbGaP
Project description:We carried out the analyses of chromosome variations between low-grade and high-grade gliomas in Chinese population. We found out the differences in chromosomes, cytobands, genes, pathways and GO functions.
2015-01-03 | GSE34888 | GEO
Project description:In this study we performed gene expression profiling of 14 cases of grade II gliomas. The results of these analysis were used in unsupervised analyses to compare correlations between the histological subtype of grade II gliomas and gene expression profiles
2010-12-31 | GSE21354 | GEO
Project description:Astrocytomas are heterogeneous intracranial glial neoplasms ranging from the highly aggressive malignant glioblastoma multiforme (GBM) to the indolent, low-grade pilocytic astrocytoma. We have investigated whether DNA microarrays can identify gene expression differences between high-grade and low-grade glial tumors. We compared the transcriptional profile of 45 astrocytic tumors including 21 GBMs and 19 pilocytic astrocytomas using oligonucleotide-based microarrays. Of the approximately 6800 genes that were analyzed, a set of 360 genes provided a molecular signature that distinguished between GBMs and pilocytic astrocytomas. Many transcripts that were increased in GBM were not previously associated with gliomas and were found to encode proteins with properties that suggest their involvement in cell proliferation or cell migration. Microarray-based data for a subset of genes was validated using real-time quantitative reverse transcription-PCR. Immunohistochemical analysis also localized the protein products of specific genes of interest to the neoplastic cells of high-grade astrocytomas. Our study has identified a large number of novel genes with distinct expression patterns in high-grade and low-grade gliomas. hanas-00078 Assay Type: Gene Expression Provider: Affymetrix Array Designs: Hu6800 Organism: Homo sapiens (ncbitax) Tissue Sites: Brain Material Types: synthetic_DNA, synthetic_RNA, organism_part Disease States: Primary Glioma, Normal
2015-06-25 | E-GEOD-70231 | biostudies-arrayexpress