Project description:Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome in which glioma is one of the most prominent tumor type. Gliomagenesis in NF1 results in heterogeneous spectrum of tumors, from low grade to high grade glioma, occurring during the entire patient lifespan. In this study, we present the molecular landscape of low- and high-grade glioma in children and adults affected by NF1 (NF1-glioma). 59 tumor samples from 56 NF1-glioma patients with 43 matched normal were profiled with Whole Exome Sequencing, DNA Methylation array (31 tumors) and RNA sequencing (29 tumors).
Project description:Mosaic Analysis with Double Markers (MADM) based glioma mouse model, which homozygously lacks Tp53 and Nf1, spontaneously developed gliomas at the post-natal 90-120 days. Tp53 and Nf1 are among the most frequently mutated genes in human glioma patients. Investigating the expression changes of genes induced by inactivation of Tp53 and Nf1 can be a clue to clarify the mechanism of gliomagenesis. We examined the expressions of glioma in MADM mouse at post-natal 150 days (n=3) and of normal brain in Tp53 and Nf1 wild type mouse at post-natal 150 days (n=2). We used SurePrint G3 Mouse GE 8×60K array slides (G4858A, Agilent Technologies).
Project description:Mosaic Analysis with Double Markers (MADM) based glioma mouse model, which homozygously lacks Tp53 and Nf1, spontaneously developed gliomas at the post-natal 90-120 days. Tp53 and Nf1 are among the most frequently mutated genes in human glioma patients. Investigating the expression changes of genes induced by inactivation of Tp53, Nf1 and EZH2 can be a clue to clarify the mechanism of gliomagenesis. We examined the expressions of glioma cells in MADM mouse (n=2), EZH2 knocked-out MADM glioma tissues (n=3) and neural stem cell (NSC), astrocyte established with normal mice brains (n=2, respectively) and TP53 knocked-out astrocytes, derived from TP53 knocked-out mice (n=2). We used SurePrint G3 Mouse GE 8×60K array slides (G4858A, Agilent Technologies).
Project description:Mosaic Analysis with Double Markers (MADM) based glioma mouse model, which homozygously lacks Tp53 and Nf1, spontaneously developed gliomas at the post-natal 90-120 days. Tp53 and Nf1 are among the most frequently mutated genes in human glioma patients. Investigating the changes of histone modifications induced by inactivation of Tp53 and Nf1 can be a clue to clarify the mechanism of gliomagenesis. We examined the histone modifications of glioma in MADM mouse at post-natal 150 days (n=3) and post-natal 8 days (n=1) and NSC, astrocyte derived from normal mice brain (both n=1) ). We used customized SurePrint G3 Mouse GE 2×400K array slides (G4858A, Agilent Technologies).
Project description:The study investigates the role of NF1 mutation and neuronal activity on the initiation of optic pathway glioma, a type of low-grade glioma. the RNAseq dataset investigates mRNA expression profile of human pilocytic astrocytomas (WHO grade I)
Project description:Glial brain tumors are composed of diverse cell types whose origins are just beginning to be unraveled. The final cellular composition of a fulminant glioma could be very different from the regulatory adaptations needed, or attempted, to establish the tumor ecosystem from an originating mutant. Using a genetically engineered mouse model that combines inducible Nf1?Trp53 loss with lineage tracing, we measured bulk and subpopulation transcriptomes during early gliomagenesis in oligodendrocyte precursor cells (OPCs). Large populations or small pools of labeled OPCs were isolated directly from their niches by laser-capture microdissection and profiled by RNA sequencing. The bulk transcriptomes of frank gliomas had relatively little in common with age-matched OPCs, but we detected generic adaptations to tumor-suppressor loss shortly after induced Nf1?Trp53 deletion. The diversity of OPCs targeted for deletion was uncovered by a stochasticprofiling fluctuation analysis of 10-cell measurements that revealed a spectrum of stem-progenitor, proneural, and mesenchymal states. Months after Nf1?Trp53 deletion, bulk differences were difficult to detect reliably, as the 10-cell data indicated several mixed-lineage states, including those not previously documented in glioma that likely marked dead-end niches. In addition, we identified a group of mutant cells devoid of conventional lineage markers, which abundantly expressed key effectors of nonsense-mediated decay and homologydependent DNA repair. In Trp53-null OPCs driven to proliferate by Nf1 deletion, ?productive? (i.e., tumorigenic) niche formation and resolution of replication stress stand out as predicted bottlenecks for glioma initiation.
Project description:We performed whole genome SNP profiling on DNA samples from 236 patients with NF1, 123 with glimoa tumors and 113 without; 117 females and 119 males, together with 29 control samples. To identify polymorphisms in human adenylate cyclase 8 (AC8) which correlate with glioma risk in NF1 in a sex-specific manner, Ac8 SNP were extracted and further analyzed for their sex-specific NF1-associated glioma risk. Three SNPs on ADCY8 were found signficant while other SNPs on CXCR7 and ADCYAP1 were promising.
Project description:We performed whole genome SNP profiling on DNA samples from 236 patients with NF1, 123 with glimoa tumors and 113 without; 117 females and 119 males, together with 29 control samples. To identify polymorphisms in human adenylate cyclase 8 (AC8) which correlate with glioma risk in NF1 in a sex-specific manner, Ac8 SNP were extracted and further analyzed for their sex-specific NF1-associated glioma risk. Three SNPs on ADCY8 were found signficant while other SNPs on CXCR7 and ADCYAP1 were promising. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from blood samples or saliva samples in three separate sets with one processed in Washington University and two in University of Utah. The data included 29 control samples and 236 NF1 patient samples (123 with and 113 without GBM) with 153 blood specimen and 97 saliva specimen.