Project description:Genome-wide DNA methylation profiling of 30 low-grade neuroepithelial tumors with FGFR1 alterations including rosette-forming glioneuronal tumor, pilocytic astrocytoma, dysembryoplastic neuroepithelial tumor, and extraventricular neurocytoma. The Illumina Infinium EPIC 850k Human DNA Methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpG sites of genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissue of 30 low-grade neuroepithelial tumors with FGFR1 alterations including kinase domain tandem duplication, in-frame fusion with TACC1, and hotspot missense mutation within the intracellular tyrosine kinase domain.
Project description:Genome-wide DNA methylation profiling of 8 low-grade neuroepithelial tumors (LGNET) with FGFR2 fusions with various histologic diagnoses including ganglioglioma, multinodular and vacuolating neuronal tumor (MVNT), low-grade glioneuronal tumor NOS, and polymorphous low-grade neuroepithelial tumor of the young (PLNTY). The Illumina Infinium EPIC 850k Human DNA Methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpG sites of genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissue of 8 low-grade neuroepithelial tumors with FGFR2 fusions.
Project description:Low grade neuroepithelial tumor is the major cause of epilepsy Low-grade neuroepithelial tumors are major causes of drug-resistant focal epilepsy. The BRAF V600E mutation is frequently observed in low grade neuroepithelial tumor and linked to poor seizure outcomes. However, its molecular role in epileptogenicity remains elusive. To understand the molecular mechanism underlying the epileptogenicity in LEAT with the BRAF V600E genetic mutation (BRAF V600E-LEAT), we conducted RNA sequencing (RNA-seq) analysis using surgical specimens of BRAF V600E-LEAT obtained and stored at a single institute. bioinformatics analysis using this dataset identified 2,134 differentially expressed genes between BRAF V600E-LEAT and control. Additionally, gene set enrichment analysis provided novel insights into the association between estrogen response-related pathways and the epileptogenicity of BRAF V600E-LEAT patients.
Project description:Pediatric neoplasms in the central nervous system show an extensive clinical and molecular heterogeneity. Molecular genetic testing contributes to accurate diagnosis and enables an optimal clinical management of affected children. Unsupervised visualization of genome-wide DNA methylation array data revealed a molecularly distinct type of pediatric high-grade neuroepithelial tumor with fusions involving the capicua transcriptional repressor (CIC) gene, with the most common fusion being CIC::LEUTX. Histopathological review demonstrated a morphologically heterogeneous group of high-grade neuroepithelial tumors with positive immunostaining for markers of glial differentiation in combination with weak and focal expression of synaptophysin, CD56 and CD99. In summary, we expand the spectrum of pediatric-type tumors of the CNS by reporting a previously uncharacterized group of rare high-grade neuroepithelial tumors that share a common DNA methylation signature and recurrent gene fusions involving the transcriptional repressor CIC.
Project description:The gene encoding fibroblast growth factor receptor 1 (FGFR1) amplification is associated with poor prognosis in estrogen receptor positive (ER+) breast cancer, and thus represents a potential therapeutic target. Fluorescent in situ hybridization (FISH) has been used as the gold standard methodology for detection of FGFR1 amplification, but it is a relatively long labor-intensive procedure and not efficient to process a large number of patient samples, especially formalin fixed paraffin embedded (FFPE) samples. This study sought to identify genes discriminative at the mRNA level for FGFR1 amplification and to construct a multi-gene test to facilitate efficient screening for FGFR1 amplified ER+ breast tumors.
Project description:We performed gene expression profiling on 151 paraffin-embedded PLGGs from different locations, ages, histological subtypes as well as BRAF genetic status We also compared molecular differences to normal pediatric brain expression profiles to observe whether those patterns were mirrored in normal brain expression. We analyzed the expression of 6,100 genes among 151 FFPE pediatric and 15 FFPE adult low-grade gliomas and analyzed how the expression patterns changes with location, age, histology and BRAF genomic status and how those differences were mirrored in normal brain expression. The values in the sample 'characteristics' columns represent; Location; SUP= Supratentorial, INF= Infratentorial Histology; PA= pilocytic astrocytoma, GG= ganglioglioma, DNT= dysembryoplastic neuroepithelial tumor, OD= oligodendroglial tumors, NOS= not otherwise specified tumors BRAF status; DUP= BRAF duplication, MUT= BRAF V600E mutation, WT= wild type, ND= not determined Primary or recurrent tumor; P=primary, R=recurrent Primary tumor that further progressed; 1=yes, 0=no, _=recurrent tumors only