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Integrative Genomic Analysis of Medulloblastoma Identiﬁes a Molecular Subgroup That Drives Poor Clinical Outcome [DNA copy number]

ABSTRACT: Integrative Genomic Analysis of Medulloblastoma Identiﬁes a Molecular Subgroup That Drives Poor Clinical Outcome [DNA copy number]

PROVIDER: PRJNA857031 | ENA |

REPOSITORIES: ENA

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Integrative Genomic Analysis of Medulloblastoma Identiﬁes a Molecular Subgroup That Drives Poor Clinical Outcome [DNA copy number]

Project description:Medulloblastomas are heterogeneous tumors that collectively represent the most common malignant brain tumor in children. To understand the molecular characteristics underlying their heterogeneity and to identify whether such characteristics represent risk factors for patients with this disease, we performed an integrated genomic analysis of a large series of primary tumors. Identified are six molecular subgroups of medulloblastoma, each with a unique combination of numerical and structural chromosomal aberrations that globally influence mRNA and miRNA expression. We reveal the relative contribution of each subgroup to clinical outcome as a whole and show that a previously unidentified molecular subgroup, characterized genetically by c-MYC copy number gains and transcriptionally by enrichment of photoreceptor pathways and increased miR-183-96-182 expression, is associated with significantly lower rates of event-free and overall survivals. Our results detail the complex genomic heterogeneity of medulloblastomas and identify a previously unrecognized molecular subgroup with poor clinical outcome for which more effective therapeutic strategies should be developed.

2022-07-10 | GSE207762 | GEO

Integrative Genomic Analysis of Medulloblastoma Identiﬁes a Molecular Subgroup That Drives Poor Clinical Outcome

2022-05-03 | GSE202043 | GEO

Integrative Genomic Analysis of Medulloblastoma Identiﬁes a Molecular Subgroup That Drives Poor Clinical Outcome

Project description:Integrative Genomic Analysis of Medulloblastoma Identiﬁes a Molecular Subgroup That Drives Poor Clinical Outcome

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Subgroup specific somatic copy number aberrations in the medulloblastoma genome

Project description:Medulloblastoma, the most common malignant pediatric brain tumour is currently treated with non-specific cytotoxic therapies including surgery, whole brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, prior attempts to identify targets for therapy have been underpowered due to small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1087 unique medulloblastomas. SCNAs are more common than SNVs in medulloblastoma, and are predominantly subgroup enriched. The most common region of focal copy number gain is a tandem duplication of the Parkinson's disease gene SNCAIP, which is exquisitely restricted to Subgroup 4alpha. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1 that arise through localized chromosomal shattering (topochromothripsis) are restricted to Group 3 tumours. Numerous actionable SCNAs, including recurrent events targeting TGFbeta signaling in Group 3, and NF-kappaB signaling in Group 4 suggest future avenues for rational, targeted therapy This SuperSeries is composed of the SubSeries listed below.

2012-07-27 | GSE37385 | GEO

Epigenetic blueprint identifies poor outcome and hypomethylating agent-responsive T-ALL subgroup

Project description:Epigenetic blueprint identifies poor outcome and hypomethylating agent-responsive T-ALL subgroup

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Subgroup specific somatic copy number aberrations in the medulloblastoma genome [gDNA]

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.

2012-07-26 | E-GEOD-37384 | biostudies-arrayexpress

Subgroup specific somatic copy number aberrations in the medulloblastoma genome [gDNA]

Project description:Affymetrix SNP6 profiling of 1087 medulloblastoma samples and 10 medulloblastoma cell lines.

2012-07-27 | GSE37384 | GEO

Subgroup specific somatic copy number aberrations in the medulloblastoma genome [mRNA]

Project description:Affymetrix Human Gene 1.1 ST Array profiling of 285 primary medulloblastoma samples. Total RNA was extracted from primary medulloblastoma samples and hybridized to Affymetrix Human Gene 1.1 ST Arrays (24-Array Plates) according to the manufacturer's instructions.

2012-07-26 | E-GEOD-37382 | biostudies-arrayexpress

Subgroup specific somatic copy number aberrations in the medulloblastoma genome [mRNA]

Project description:Affymetrix Human Gene 1.1 ST Array profiling of 285 primary medulloblastoma samples.

2012-07-27 | GSE37382 | GEO

A mouse model of the most aggressive subgroup of human medulloblastoma

Project description:This SuperSeries is composed of the following subset Series: GSE33199: A mouse model of the most aggressive subgroup of human medulloblastoma [Mouse430_2] GSE33200: A mouse model of the most aggressive subgroup of human medulloblastoma [HT_MG-430_PM] Refer to individual Series

2012-02-29 | E-GEOD-33201 | biostudies-arrayexpress

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