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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE34280 | GEO | 2011/12/09

SECONDARY ACCESSION(S): PRJNA156527

REPOSITORIES: GEO

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

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.

2011-12-09 | E-GEOD-34280 | biostudies-arrayexpress

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

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2011-12-13 | E-GEOD-34355 | biostudies-arrayexpress

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

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Project description:Affymetrix Human Gene 2.0 ST Array profiling of 9 pairs of matched primary-metastases medulloblastoma samples. Total RNA was extracted from primary and metastases medulloblastoma samples and hybridized to Affymetrix Human Gene 2.0 ST Arrays (24-Array Plates) according to the manufacturer's instructions.

2015-04-01 | E-GEOD-63668 | biostudies-arrayexpress

DNA methylation of matched primary-metastases medulloblastomas

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Expression data of endothelial cells from mouse hindbrain and genetic Wnt-medulloblastoma and Shh-medulloblastoma mouse models

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