Medulloblastoma is the most common malignant pediatric brain tumor, and mechanisms underlying its development are poorly understood. We identified recurrent amplification of the miR-17/92 polycistron proto-oncogene in 6% of pediatric medulloblastomas by high-resolution single-nucleotide polymorphism genotyping arrays and subsequent interphase fluorescence in situ hybridization on a human medulloblastoma tissue microarray. Profiling the expression of 427 mature microRNAs (miRNA) in a series of 90 primary human medulloblastomas revealed that components of the miR-17/92 polycistron are the most highly up-regulated miRNAs in medulloblastoma. Expression of miR-17/92 was highest in the subgroup of medulloblastomas associated with activation of the sonic hedgehog (Shh) signaling pathway compared with other subgroups of medulloblastoma. Medulloblastomas in which miR-17/92 was up-regulated also had elevated levels of MYC/MYCN expression. Consistent with its regulation by Shh, we observed that Shh treatment of primary cerebellar granule neuron precursors (CGNP), proposed cells of origin for the Shh-associated medulloblastomas, resulted in increased miR-17/92 expression. In CGNPs, the Shh effector N-myc, but not Gli1, induced miR-17/92 expression. Ectopic miR-17/92 expression in CGNPs synergized with exogenous Shh to increase proliferation and also enabled them to proliferate in the absence of Shh. We conclude that miR-17/92 is a positive effector of Shh-mediated proliferation and that aberrant expression/amplification of this miR confers a growth advantage to medulloblastomas.
The miR-17/92 polycistron is up-regulated in sonic hedgehog-driven medulloblastomas and induced by N-myc in sonic hedgehog-treated cerebellar neural precursors.
Sex, Age, Specimen part
View SamplesPrimitive neuro-ectodermal tumours (PNET) of the supratentorial region are rare, highly malignant embryonal brain tumours affecting young children. We recently highlighted the importance of a microRNA cluster housing miR-520g. We utilized the Illumina HumanWG-6 v3 R2 and HumanHT-12 v3 R2 Expression BeadChip platforms to profile the effects of miR-520g on gene expression.
Frequent amplification of a chr19q13.41 microRNA polycistron in aggressive primitive neuroectodermal brain tumors.
Specimen part, Cell line
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Medulloblastoma subgroups remain stable across primary and metastatic compartments.
Sex, Age, Specimen part, Subject
View SamplesAffymetrix Human Gene 2.0 ST Array profiling of 9 pairs of matched primary-metastases medulloblastoma samples.
Medulloblastoma subgroups remain stable across primary and metastatic compartments.
Sex, Age, Specimen part, Subject
View SamplesGene expression (mRNA) profiling of human ependymomas
Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma.
Sex, Age, Specimen part
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Differential glucose requirement in skin homeostasis and injury identifies a therapeutic target for psoriasis.
Age, Specimen part
View SamplesGlut1 is highly expressed in basal cells of keratinocytes, but the functions and regulation of Glut1 has not been explored, here we specifically ablate Glut1 in epidermal keratinocytes to elucidate the role of glucose transport in the skin.
Differential glucose requirement in skin homeostasis and injury identifies a therapeutic target for psoriasis.
Age, Specimen part
View SamplesThe pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and its relationship to other lymphomas are largely unknown. This is partly due to the technical challenge of analyzing its rare neoplastic L&H cells, which are dispersed in an abundant non-neoplastic cellular microenvironment. We performed a genome-wide expression study of microdissected lymphocytic and histiocytic (L&H) lymphoma cells in comparison to normal and other malignant B cells, which indicates a relationship of L&H cells to and/or origin from germinal center B cells at transition to memory B cells. L&H cells show a surprisingly high similarity to the tumor cells of T cell-rich B cell lymphoma and classical Hodgkin lymphoma, a partial loss of their B cell phenotype and deregulation of many apoptosis-regulators and putative oncogenes. Importantly, L&H cells are characterized by constitutive NF-B activity and aberrant ERK signaling. Thus, these findings shed new light on the nature of L&H cells, revealed several novel pathogenetic mechanisms in NLPHL, and may help in differential diagnosis and lead to novel therapeutic strategies.
Origin and pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma as revealed by global gene expression analysis.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Stem cell gene expression programs influence clinical outcome in human leukemia.
Specimen part
View SamplesExperiments using xenografts show that some solid tumours and leukemias are organized as cellular hierarchies sustained by cancer stem cells (CSC). Despite promise, the relevance of the CSC model to human disease remains uncertain. Here we show that acute myeloid leukemia (AML) follows a CSC model based on sorting multiple populations from each of 16 primary human AML samples and identifying which contain leukemia stem cells (LSC) using a sensitive xenograft assay. Analysis of gene expression from all functionally validated populations yielded an LSC-specific signature. Similarly, a hematopoietic stem cell (HSC) gene signature was established. Bioinformatic analysis identified a core transcriptional program shared by LSC and HSC, revealing the molecular machinery underlying stemness properties. Both stem cell programs were highly significant independent predictors of patient survival and also found in existing prognostic signatures. Thus, determinants of stemness influence clinical outcome of AML establishing that LSC are clinically relevant and not mere artifacts of xenotransplantation.
Stem cell gene expression programs influence clinical outcome in human leukemia.
No sample metadata fields
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