Browse
Submit Data
Databases
API
Help

Dataset Information

9 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Adult grade II astrocytomas are genetically distinct from their pediatric counterparts, and display a more stem cell-like expression pattern linked with more aggressive behaviour

ABSTRACT: We have used microarray comparative genomic hybridization (aCGH) at 1Mb resolution to study copy number changes in a series of WHO Grade II Astrocytomas (n=21). We have used Illumina arrays to study genome-wide expression patterns in a series of WHO Grade II Astrocytomas (n=10). Keywords: Array Comparative Genomic Hybridization (aCGH), Expression microarray [aCGH]: Single hybridization per case. 21 astrocytomas WHO grade II were analyzed. Target (tumor) labelled with Cy5 and reference with Cy3. Mixture of 20 normal male or female genomic DNA was used in sex-mismatched hybridization. [mRNA]: Single hybridization per case. 10 astrocytomas WHO grade II were analyzed (5 adult, 5 pediatric)

ORGANISM(S): Homo sapiens

SUBMITTER: Jones David

PROVIDER: S-ECPF-GEOD-23869 | biostudies-other |

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Adult grade II astrocytomas are genetically distinct from their pediatric counterparts, and display a more stem cell-like expression pattern linked with more aggressive behaviour

2010-08-31 | GSE23869 | GEO

Adult grade II astrocytomas are genetically distinct from their pediatric counterparts, and display a more stem cell-like expression pattern linked with more aggressive behaviour

Project description:We have used microarray comparative genomic hybridization (aCGH) at 1Mb resolution to study copy number changes in a series of WHO Grade II Astrocytomas (n=21). We have used Illumina arrays to study genome-wide expression patterns in a series of WHO Grade II Astrocytomas (n=10). Keywords: Array Comparative Genomic Hybridization (aCGH), Expression microarray [aCGH]: Single hybridization per case. 21 astrocytomas WHO grade II were analyzed. Target (tumor) labelled with Cy5 and reference with Cy3. Mixture of 20 normal male or female genomic DNA was used in sex-mismatched hybridization. [mRNA]: Single hybridization per case. 10 astrocytomas WHO grade II were analyzed (5 adult, 5 pediatric)

2010-08-30 | E-GEOD-23869 | biostudies-arrayexpress

World Health Organization grade II-III astrocytomas consist of genetically distinct tumor lineages.

Project description:Recent investigations revealed genetic analysis provides important information in management of gliomas, and we previously reported grade II-III gliomas could be classified into clinically relevant subgroups based on the DNA copy number aberrations (CNAs). To develop more precise genetic subgrouping, we investigated the correlation between CNAs and mutational status of the gene encoding isocitrate dehydrogenase (IDH) of those tumors. We analyzed the IDH status and CNAs of 174 adult supratentorial gliomas of astrocytic or oligodendroglial origin by PCR-based direct sequencing and comparative genomic hybridization, respectively. We analyzed the relationship between genetic subclassification and clinical features. We found the most frequent aberrations in IDH mutant tumors were the combined whole arm-loss of 1p and 19q (1p/19q codeletion) followed by gain on chromosome arm 7q (+7q). The gain of whole chromosome 7 (+7) and loss of 10q (-10q) were detected in IDH wild-type tumors. Kaplan-Meier estimates for progression-free survival showed that the tumors with mutant IDH, -1p/19q, or +7q (in the absence of +7p) survived longer than tumors with wild-type IDH, +7, or -10q. As tumors with +7 (IDH wild-type) showed a more aggressive clinical nature, they are probably not a subtype that developed from the slowly progressive tumors with +7q (IDH mutant). Thus, tumors with a gain on chromosome 7 (mostly astrocytic) comprise multiple lineages, and such differences in their biological nature should be taken into consideration during their clinical management.

| S-EPMC4982592 | biostudies-literature

ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grade astrocytomas.

Project description:BackgroundHigh-grade (WHO grade III and IV) astrocytomas are aggressive malignant brain tumors affecting humans with a high risk of recurrence in both children and adults. To date, limited information is available on the genetic and molecular alterations important in the onset and progression of pediatric high-grade astrocytomas and, even less, on the prognostic factors that influence long-term outcome in children with recurrence. A-to-I RNA editing is an essential post-transcriptional mechanism that can alter the nucleotide sequence of several RNAs and is mediated by the ADAR enzymes. ADAR2 editing activity is particularly important in mammalian brain and is impaired in both adult and pediatric high-grade astrocytomas. Moreover, we have recently shown that the recovered ADAR2 activity in high-grade astrocytomas inhibits in vivo tumor growth. The aim of the present study is to investigate whether changes may occur in ADAR2-mediated RNA editing profiles of relapsed high-grade astrocytomas compared to their respective specimens collected at diagnosis, in four pediatric patients.MethodsTotal RNAs extracted from all tumor samples and controls were tested for RNA editing levels (by direct sequencing on cDNA pools) and for ADAR2 mRNA expression (by qRT-PCR).ResultsA significant loss of ADAR2-editing activity was observed in the newly diagnosed and recurrent astrocytomas in comparison to normal brain. Surprisingly, we found a substantial rescue of ADAR2 editing activity in the relapsed tumor of the only patient showing prolonged survival.ConclusionsHigh-grade astrocytomas display a generalized loss of ADAR2-mediated RNA editing at both diagnosis and relapse. However, a peculiar Case, in complete remission of disease, displayed a total rescue of RNA editing at relapse, intriguingly suggesting ADAR2 activity/expression as a possible marker for long-term survival of patients with high-grade astrocytomas.

| S-EPMC3663793 | biostudies-literature

Array-CGH screening of pediatric low-grade astrocytomas (n=66)

Project description:DNA copy-number profiling of 66 astrocytomas of WHO °I or °II Keywords: Genetic modification

2007-08-10 | GSE8737 | GEO

Array-CGH screening of pediatric low-grade astrocytomas (n=66)

Project description:DNA copy-number profiling of 66 astrocytomas of WHO °I or °II Comparison of tumor DNA (tumor) versus control DNA (pool of lymphocyte DNA from 10 healthy donors). Whole-genome screening for DNA copy-number aberrations using array-based comparative genomic hybridization (aCGH). Tumor DNA labeled in Cy3 and control DNA labeled in Cy5.

2007-08-10 | E-GEOD-8737 | biostudies-arrayexpress

Evolutionary etiology of high-grade astrocytomas.

Project description:Glioblastoma (GBM), the most common brain malignancy, remains fatal with no effective treatment. Analyses of common aberrations in GBM suggest major regulatory pathways associated with disease etiology. However, 90% of GBMs are diagnosed at an advanced stage (primary GBMs), providing no access to early disease stages for assessing disease progression events. As such, both understanding of disease mechanisms and the development of biomarkers and therapeutics for effective disease management are limited. Here, we describe an adult-inducible astrocyte-specific system in genetically engineered mice that queries causation in disease evolution of regulatory networks perturbed in human GBM. Events yielding disease, both engineered and spontaneous, indicate ordered grade-specific perturbations that yield high-grade astrocytomas (anaplastic astrocytomas and GBMs). Impaired retinoblastoma protein RB tumor suppression yields grade II histopathology. Additional activation of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) network drives progression to grade III disease, and further inactivation of phosphatase and tensin homolog (PTEN) yields GBM. Spontaneous missense mutation of tumor suppressor Trp53 arises subsequent to KRAS activation, but before grade III progression. The stochastic appearance of mutations identical to those observed in humans, particularly the same spectrum of p53 amino acid changes, supports the validity of engineered lesions and the ensuing interpretations of etiology. Absence of isocitrate dehydrogenase 1 (IDH1) mutation, asymptomatic low grade disease, and rapid emergence of GBM combined with a mesenchymal transcriptome signature reflect characteristics of primary GBM and provide insight into causal relationships.

| S-EPMC3816471 | biostudies-literature

A brain-penetrant RAF dimer antagonist for the noncanonical BRAF oncoprotein of pediatric low-grade astrocytomas.

Project description:Background:Activating mutations or structural rearrangements in BRAF are identified in roughly 75% of all pediatric low-grade astrocytomas (PLGAs). However, first-generation RAF inhibitors approved for adult melanoma have poor blood-brain penetrance and are only effective on tumors that express the canonical BRAFV600E oncoprotein, which functions as a monomer. These drugs (type I antagonists that target the "DFG-in" conformation of the kinase) fail to block signaling via KIAA1549:BRAF, a truncation/fusion BRAF oncoprotein which functions as a dimer and is found in the most common form of PLGA. Methods:A panel of small molecule RAF inhibitors (including type II inhibitors, targeting the "DFG-out" conformation of the kinase) was screened for drugs showing efficacy on murine models of PLGA and on authentic human PLGA cells expressing KIAA1549:BRAF. Results:We identify a type II RAF inhibitor that serves as an equipotent antagonist of BRAFV600E, KIAA1549:BRAF, and other noncanonical BRAF oncoproteins that function as dimers. This drug (MLN2480, also known as TAK-580) has good brain penetrance and is active on authentic human PLGA cells in brain organotypic cultures. Conclusion:MLN2480 may be an effective therapeutic for BRAF mutant pediatric astrocytomas.

| S-EPMC5464455 | biostudies-literature

High-grade gliomas in adolescents and young adults highlight histomolecular differences from their adult and pediatric counterparts.

Project description:BackgroundConsidering that pediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs).MethodsWe performed a multicentric retrospective study of 112 AYAs from adult and pediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyze their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25 years, histopathological HGG diagnosis, available clinical data, and preoperative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next-generation sequencing, whole exome sequencing, and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 World Health Organization (WHO) classification.ResultsBased on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of pediatric subtypes (histone H3-mutants, 40%) but also adult subtypes (isocitrate dehydrogenase [IDH] mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH mutants, and 1p/19q codeletion and the relative high frequency of "rare adult IDH mutations" (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to what is observed in children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance.ConclusionsHGGs in AYAs could benefit from a specific classification, driven by molecular subtyping rather than age group. Collaborative efforts are needed from pediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.

| S-EPMC7594566 | biostudies-literature

Inducible Astrocytomas in Genetically Engineered Mice

Project description:This SuperSeries is composed of the SubSeries listed below.

2012-09-13 | GSE26069 | GEO