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Series GSE4840 Query DataSets for GSE4840
Status Public on Jun 27, 2006
Title Metastatic potential of melanomas defined by specific gene expression profiles with no BRAF signature (Zürich).
Organism Homo sapiens
Experiment type Expression profiling by array
Summary 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.
Keywords: class discovery study (differential metastatic potential)
Overall design In this (Zürich) data set three melanocyte cultures and twelve melanoma cultures were analyzed.
Contributor(s) Hoek KS, Schlegel NC, Brafford P, Sucker A, Ugurel S, Kumar R, Weber BL, Nathanson KL, Phillips DJ, Herlyn M, Schadendorf D, Dummer R
Citation(s) 16827748, 19213840
Submission date May 15, 2006
Last update date Nov 08, 2019
Contact name Keith S Hoek
Organization name Currently unaffilliated
Street address private
City Zürich
ZIP/Postal code 8004
Country Switzerland
Platforms (2)
GPL96 [HG-U133A] Affymetrix Human Genome U133A Array
GPL97 [HG-U133B] Affymetrix Human Genome U133B Array
Samples (30)
GSM108371 M980513_A
GSM108372 M990115_A
GSM108373 M000216_A
This SubSeries is part of SuperSeries:
GSE4845 Metastatic potential of melanomas defined by specific gene expression profiles with no BRAF signature.
BioProject PRJNA104551

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