ABSTRACT: This study contains tumor DNA (with matched normal) for 1 medulloblastoma and 1 ependymoma patient. Tumor RNA sequencing data is also present for the medulloblastoma patient
Project description:This dataset contains DNA and RNA sequencing information for AML, Gliomas, brain tumors (medulloblastoma and ependymoma), DIPG, rhabdoid tumors and soft tissue sarcomas. In total 39 samples are present (14 matched normal, 25 tumor samples). Not all samples have matched normals and not all samples have RNA sequencing data..
Project description:Characterizing the impact of pharmacological and shRNA-mediated silencing of EAG2 in medulloblastoma. Medulloblastoma (MB) is the most common pediatric CNS malignancy. Previously, we demonstrated that overexpression of the ion channel EAG2, identified in a subset of histological and molecular subtypes of this disease, functionally contributes to tumor progression (PMID: 22855790). Here, we demonstrate the evolutionarily conserved function of EAG2 potassium channel in promoting brain tumor growth and metastasis, delineate downstream pathways and uncover a co-option mechanism for different potassium channels to regulate mitotic cell volume and tumor progression. We show that EAG2 potassium channel is enriched at the trailing edge of migrating MB cells to regulate local cell volume dynamics, thereby facilitating cell motility. We identify the FDA- approved antipsychotic drug thioridazine as an EAG2 channel blocker that reduces xenografted MB growth and metastasis, and present a case report of repurposing thioridazine for treating a human patient. Our findings thus illustrate the potential of targeting ion channels in cancer treatment.
Project description:The hypothesis was that the orthotopic xenograft model of ependymoma faithfully recapitulate the genomics signatures of the original tumor patient tissue
Project description:This phase I trial studies the side effects and best dose of pembrolizumab and to see how well it works in treating younger patients with high-grade gliomas (brain tumors that are generally expected to be fast growing and aggressive), diffuse intrinsic pontine gliomas (brain stem tumors), brain tumors with a high number of genetic mutations, ependymoma or medulloblastoma that have come back (recurrent), progressed, or have not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may induce changes in the body’s immune system, and may interfere with the ability of tumor cells to grow and spread.
Project description:The hypothesis was that the orthotopic xenograft model of ependymoma faithfully recapitulate the genomics signatures of the original tumor patient tissue Original tumor cells were implanted into the same location of SCID mice and check for transcriptome profiles upon subsequent passages to show that the passages preserve the overall genomics signature of the original tumor tissue.
Project description:Genomic rearrangements typically occur progressively during tumor development. Recent findings, however, suggest an alternative mechanism, involving chromosome shattering and reshuffling ('chromothripsis'), for which no genetic basis has yet been described. Whole-genome sequencing of a Sonic-Hedgehog medulloblastoma (SHH-MB) brain tumor from a patient with a germline TP53 mutation (Li-Fraumeni syndrome) revealed massive, complex rearrangements resulting from chromothripsis. Integrating TP53 status with genomic rearrangement data in additional medulloblastomas revealed a striking association between TP53 mutation and chromothripsis in SHH-MBs. Unexpectedly, five seemingly sporadic SHH-MB patients with chromothripsis harbored TP53 germline mutations – findings relevant for clinical management. Analysis of additional tumor entities substantiated a link between TP53 mutation and chromothripsis, beyond general genomic instability. Among these, we observed a strong association between somatic TP53 mutations and chromothripsis in acute myeloid leukemia. These findings implicate p53 in the initiation of, or cellular reaction to, chromothripsis – a novel role for the 'guardian of the genome'. The DNA copy-number profiles of 11 primary medulloblastoma samples were analyzed on the Affymetrix Mapping250K Nsp array, together with data from 70 primary samples taken from GSE21140. Data from diploid reference samples were taken from GSE9222. Additionally, DNA copy-number profiles for 19 additional medulloblastoma samples were generated on the Affymetrix SNP6 platform with matched blood samples.
Project description:Molecular characterization of medulloblastoma (MB) cell origin and properties is the basis for a well-defined classification system. However, limited data is available regarding the MB tumor microenvironment. Here we present a mass spectrometry-based multi-omics study of cerebrospinal fluid (CSF) from recurrent MB patients. A group of age-matched patients without a neoplastic disease was used as control cohort. Proteome profiling identified several characteristic tumor markers and revealed a strong prevalence of anti-inflammatory and tumor-promoting proteins characteristic for alternatively polarized myeloid cells in MB samples. The up-regulation of ADAMTS1, GAP43 and GPR37 indicated hypoxia in CSF of MB patients. This notion was independently supported by metabolomics, demonstrating up-regulation of tryptophan, methionine, serine and lysine, all of which have been described to be induced upon hypoxia in CSF. The beta-oxidation promoting lipid hormone 12,13-DiHOME was found strongly upregulated, potentially promoting a metabolic shift supporting drug resistance and stem cell properties of MB cells.
