Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human melanomas to determine metastatic potential defined by specific gene expression profiles with no BRAF signature.

ABSTRACT: The molecular biology of metastatic potential in melanoma has been studied many times previously and changes in the expression of many genes have been linked to metastatic behaviour. What is lacking is a systematic characterization of the regulatory relationships between genes whose expression is related to metastatic potential. Such a characterization would produce a molecular taxonomy for melanoma which could feasibly be used to identify epigenetic mechanisms behind changes in metastatic behaviour. To achieve this we carried out three separate DNA microarray analyses on a total of 86 cultures of melanoma. Significantly, multiple testing correlation revealed that previous reports describing correlations of gene expression with activating mutations in BRAF or NRAS were incorrect and that no gene expression patterns correlate with the mutation status of these MAPK pathway components. Instead, we identified three different sample cohorts (A, B and C) and found that these cohorts represent melanoma groups of differing metastatic potential. Cohorts A and B were susceptible to TGFbeta-mediated inhibition of proliferation and had low motility. Cohort C was resistant to TGFb and demonstrated high motility. Meta-analysis of the data against previous studies linking gene expression and phenotype confirmed that cohorts A and C represent transcription signatures of weakly and strongly metastatic melanomas, respectively. Gene expression co-regulation suggested that signalling via TGFbeta-type and Wnt pathways underwent considerable change between cohorts. These results suggest a model for the transition from weakly to strongly metastatic melanomas in which TGFbeta-type signalling upregulates genes expressing vasculogenic/extracellular matrix remodeling factors and Wnt signal inhibitors, coinciding with a downregulation of genes downstream of Wnt signalling. This SuperSeries is composed of the following subset Series:; GSE4840: (ZÃ¼rich data set). GSE4841: (Philadelphia data set). GSE4843: (Mannheim data set). Experiment Overall Design: Refer to individual Series Experiment Overall Design: Zurich: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4840 Experiment Overall Design: Philadelphia: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4841 Experiment Overall Design: Mannheim: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4843

ORGANISM(S): Homo sapiens

SUBMITTER: Keith Hoek

PROVIDER: E-GEOD-4845 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Metastatic potential of melanomas defined by specific gene expression profiles with no BRAF signature.

Hoek Keith S KS Schlegel Natalie C NC Brafford Patricia P Sucker Antje A Ugurel Selma S Kumar Rajiv R Weber Barbara L BL Nathanson Katherine L KL Phillips David J DJ Herlyn Meenhard M Schadendorf Dirk D Dummer Reinhard R

Pigment cell research 20060801 4

The molecular biology of metastatic potential in melanoma has been studied many times previously and changes in the expression of many genes have been linked to metastatic behaviour. What is lacking is a systematic characterization of the regulatory relationships between genes whose expression is related to metastatic potential. Such a characterization would produce a molecular taxonomy for melanoma which could feasibly be used to identify epigenetic mechanisms behind changes in metastatic behav ...[more]

PMID: 16827748

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Dataset Information

Transcription profiling of human melanomas to determine metastatic potential defined by specific gene expression profiles with no BRAF signature.

Publications

Metastatic potential of melanomas defined by specific gene expression profiles with no BRAF signature.

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