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Clonal Selection Drives Genetic Divergence of Metastatic Medulloblastoma

ABSTRACT: 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

ORGANISM(S): Homo sapiens

SUBMITTER: Paul Northcott

PROVIDER: E-GEOD-34356 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Homo sapiens

Project description:Clonal Selection Drives Genetic Divergence of Metastatic Medulloblastoma [Affymetrix SNP6 Arrays]

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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.

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Clonal Selection Drives Genetic Divergence of Metastatic Medulloblastoma [Illumina Infinium HumanMethylation27 Beadchip v1.2]

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

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