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Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas

ABSTRACT: Pilocytic astrocytomas (PAs), WHO Grade I, are one of the most frequently occurring childhood brain tumors. We have used microarray comparative genomic hybridization (aCGH) to study copy number changes on chromosome 7 in a series of PAs (n=44). Keywords: Comparative Genomic Hybridization

ORGANISM(S): Homo sapiens

PROVIDER: GSE11265 | GEO | 2009/04/15

SECONDARY ACCESSION(S): PRJNA106663

REPOSITORIES: GEO

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Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas

Project description:Pilocytic astrocytomas (PAs), WHO Grade I, are one of the most frequently occurring childhood brain tumors. We have used microarray comparative genomic hybridization (aCGH) to study copy number changes on chromosome 7 in a series of PAs (n=44). Keywords: Comparative Genomic Hybridization Single hybridization per case. 44 pilocytic astrocytomas WHO grade I 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.

2009-04-15 | E-GEOD-11265 | biostudies-arrayexpress

Array-based comparative genomic hybridisation analysis at 1Mb resolution of 44 pilocytic astrocytomas

2008-04-28 | GSE11263 | GEO

Array-based comparative genomic hybridisation analysis at 1Mb resolution of 44 pilocytic astrocytomas

Project description:Pilocytic astrocytomas (PAs), WHO Grade I, are one of the most frequently occurring childhood brain tumors. We have used microarray comparative genomic hybridization (aCGH) at 1Mb resolution to study copy number changes in a series of PAs (n=44). Single hybridization per case. 44 pilocytic astrocytomas WHO grade I 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.

2008-04-28 | E-GEOD-11263 | biostudies-arrayexpress

DNA methylation analysis of paediatric pilocytic and diffuse astrocytomas

Project description:Paediatric low-grade gliomas (LGGs) account for about a third of all brain tumours in children. We conducted a detailed study of DNA methylation to improve our understanding of the biology of pilocytic and diffuse astrocytomas. Comparisons were performed between tumours and normal brain controls from matching location, and between pilocytic and diffuse astrocytomas. Pilocytic astrocytomas were found to have a distinctive signature involving 315 CpG sites, with the majority of the sites (312 CpG sites) hypomethylated in pilocytic astrocytomas. Additionally many of the sites were located within annotated enhancers. The distinct signature in pilocytic astrocytomas was not present in diffuse astrocytomas or in published profiles of other brain tumours and normal brain tissue. On further analysis of the 315 CpG sites, the AP-1 transcription factor complex was predicted to bind within 200bp of a subset of teh 315 differentially methylated CpG sites. We also observed up-regulation of the AP-1 factors, FOS and FOSL1 in pilocytic astrocytomas. Our findings highlight novel epigenetic differences between pilocytic and diffuse astrocytomas, in addition to well-described alterations involving BRAF, MYB and FGFR1.

2016-05-10 | GSE77241 | GEO

Pilocytic astrocytoma

Project description:Pilocytic astrocytomas (PAs) are the most common glioma in children. While many PAs are slow growing or clinically indolent, others exhibit more aggressive features with tumor recurrence and death. In order to identify genetic signatures that might predict PA clinical behavior, we performed gene expression profiling on 41 primary PAs arising sporadically and in patients with neurofibromatosis type 1 (NF1). While no expression signature was found that could discriminate clinically-aggressive or recurrent tumors from more indolent cases, PAs arising in patients with NF1 did exhibit a unique gene expression pattern. In addition, we identified a gene expression signature that stratified PAs by location (supratentorial versus infratentorial). Keywords: Human, WHO grade I, Brain tumor, Pilocytic astrocytoma, NF1

2007-03-14 | GSE5675 | GEO

Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas.

Project description:Brain tumors are the most common solid tumors of childhood, and pilocytic astrocytomas (PA) are the most common central nervous system tumor in 5 to 19 year olds. Little is known about the genetic alterations underlying their development. Here, we describe a tandem duplication of approximately 2 Mb at 7q34 occurring in 66% of PAs. This rearrangement, which was not observed in a series of 244 higher-grade astrocytomas, results in an in-frame fusion gene incorporating the kinase domain of the BRAF oncogene. We further show that the resulting fusion protein has constitutive BRAF kinase activity and is able to transform NIH3T3 cells. This is the first report of BRAF activation through rearrangement as a frequent feature in a sporadic tumor. The frequency and specificity of this change underline its potential both as a therapeutic target and as a diagnostic tool.

| S-EPMC2577184 | biostudies-literature

Transcription profiling of human pilocytic astrocytoma to develop molecular signatures

Project description:Pilocytic astrocytomas (PAs) are the most common glioma in children. While many PAs; are slow growing or clinically indolent, others exhibit more aggressive features with tumor; recurrence and death. In order to identify genetic signatures that might predict PA clinical; behavior, we performed gene expression profiling on 41 primary PAs arising sporadically and in; patients with neurofibromatosis type 1 (NF1). While no expression signature was found that; could discriminate clinically-aggressive or recurrent tumors from more indolent cases, PAs; arising in patients with NF1 did exhibit a unique gene expression pattern. In addition, we; identified a gene expression signature that stratified PAs by location (supratentorial versus; infratentorial). Experiment Overall Design: 41 pilocytic astrocytoma samples were analyzed.

2008-06-14 | E-GEOD-5675 | biostudies-arrayexpress

Single cell RNA-seq of BRAF-rearranged pilocytic astrocytomas

Project description:Single cell RNA-seq of BRAF-rearranged pilocytic astrocytomas

| PRJNA551047 | ENA

Single cell RNA-seq of BRAF-rearranged pilocytic astrocytomas

Project description:Single cell RNA-seq of BRAF-rearranged pilocytic astrocytomas

| PRJNA551048 | ENA

MicroRNA profile of pediatric pilocytic astrocytomas identifies two tumor-specific signatures when compared to non-neoplastic white matter

Project description:Pilocytic astrocytoma (PA) is a low-grade neoplasm frequently found in childhood. PA is characterized by slow growth and a relatively good prognosis. Genetic mechanisms such as activation of MAPK, BRAF gene deregulation and neurofibromatosis type 1 (NF1) syndrome have been associated with PA development. Epigenetic signature and miRNA expression profile are providing new insights about different types of tumor, including PAs. In the present study we evaluated global miRNA expression in 16 microdissected pediatric PA specimens, three NF1-associated PAs and 11 cerebral white matter (WM) samples by the microarray method. An additional cohort of 20 PAs was used to validate by qRT-PCR the expression of six miRNAs differentially expressed in the microarray data. Unsupervised hierarchical clustering analysis distinguished one cluster with nine PAs, including all NF1 cases and a second group consisting of the WM samples and seven PAs. Among 88 differentially expressed miRNAs between PAs and WM samples, the most underexpressed ones regulate classical pathways of tumorigenesis, while the most overexpressed miRNAs are related to pathways such as focal adhesion, P53 signaling pathway and gliomagenesis. The PAs/NF1 presented a subset of underexpressed miRNAs, which was also associated with known deregulated pathways in cancer such as cell cycle and hippo pathway. In summary, our data demonstrate that PA harbors at least two distinct miRNA signatures, including a subgroup of patients with NF1/PA lesions.

2019-08-01 | GSE135189 | GEO

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