Project description:This SuperSeries is composed of the following subset Series: GSE34280: Clonal Selection Drives Genetic Divergence of Metastatic Medulloblastoma [Affymetrix SNP6 Arrays] GSE34355: Clonal Selection Drives Genetic Divergence of Metastatic Medulloblastoma [Illumina Infinium HumanMethylation27 Beadchip v1.2] Refer to individual Series
Project description:Medulloblastoma, the most common malignant pediatric brain tumour, disseminates by shedding cells into the cerebrospinal fluid, which then re-implant to cover the surface of the brain and spinal cord. Metastases are a very poor prognostic sign at presentation and are usually lethal at recurrence. Mechanisms driving dissemination have been described in the bulk primary tumour, with the underlying assumption that primary tumour and metastases are biologically similar. Here we show that in both mouse and human medulloblastoma, multiple metastases from a single animal are extremely similar, but are genetically highly divergent from the primary tumour. Clonal genetic events in the metastases can be demonstrated in a restricted sub-clone of the primary tumour, suggesting that only rare cells within the primary tumour have the ability to metastasize. Failure to account for the bicompartmental nature of primary and metastatic medulloblastoma represents a major barrier to the development of effective targeted therapies. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved human medulloblastoma tissue samples. Copy number analysis of Affymetrix SNP6 arrays was performed for 17 pediatric medulloblastoma samples. Samples comprise a series of 7 patient-matched primary/metastatic cases.
Project description:Affymetrix SNP6 profiling of 1087 medulloblastoma samples and 10 medulloblastoma cell lines. Genomic DNA was extracted from primary medulloblastoma samples and medulloblastoma cell lines and hybridized to Affymetrix SNP6 arrays according to the manufacturer's instructions.
Project description:AIMAH is an ACTH-independent bilateral enlargement of the adrenal cortex occuring during adulthood. The enlargment is related to the growth of multiple benign nodules. This condition is associated with various degrees of cortisol hypersecretion. The occurence of several nodules in both adrenals, and the existence of familial forms, suggest the existence of a germline genetic predisposition. To find the gene(s), the aim of the project was to look for recurrent chromosomal alterations in the AIMAH nodules. Extensive mapping of somatic gains, losses and copy-neutral loss of heterozygosity (LOH) was performed with Affymetrix SNP6 arrays. A copy neutral LOH of 16p, occuring in 7 of 26 patients, was one of the only recurrent alterations, pointing towards a candidate gene in this region. Of note this condition differs from the congenital adrenal hyperplasias, related to genetic alterations of steroidogenesis (the latter is an ACTH dependent adrenal hyperplasia). Affymetrix SNP6 arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved tumor samples or peripheral blood samples.
Project description:Medulloblastoma, the most common malignant pediatric brain tumour, disseminates by shedding cells into the cerebrospinal fluid, which then re-implant to cover the surface of the brain and spinal cord. Metastases are a very poor prognostic sign at presentation and are usually lethal at recurrence. Mechanisms driving dissemination have been described in the bulk primary tumour, with the underlying assumption that primary tumour and metastases are biologically similar. Here we show that in both mouse and human medulloblastoma, multiple metastases from a single animal are extremely similar, but are genetically highly divergent from the primary tumour. Clonal genetic events in the metastases can be demonstrated in a restricted sub-clone of the primary tumour, suggesting that only rare cells within the primary tumour have the ability to metastasize. Failure to account for the bicompartmental nature of primary and metastatic medulloblastoma represents a major barrier to the development of effective targeted therapies. DNA methylation analysis of 15 pediatric medulloblastoma samples consisting of 6 primary-metastatic pairs and 4 normal cerebella samples profiled in Illumina Infinium HumanMethylation27 Beadchip v1.2