Microarray expression profiling in melanoma reveals a BRAF mutation signature

Pavey, Sandra, Johansson, Peter, Packer, Leisl, Taylor, Jennifer, Stark, Mitchell, Pollock, Pamela M., Walker, Graeme J., Boyle, Glen M., Harper, Ursula, Cozzi, Sarah-Jane, Hansen, Katherine, Yudt, Laura, Schmidt, Chris, Hersey, Peter, Ellem, Kay, O'Rourke, Michael, Parsons, Peter G., Meltzer, Paul S., Ringner, Markus, & Hayward, Nicholas K. (2004) Microarray expression profiling in melanoma reveals a BRAF mutation signature. Oncogene, 23(23), pp. 4060-4067.

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We have used microarray gene expression profiling and machine learning to predict the presence of BRAF mutations in a panel of 61 melanoma cell lines. The BRAF gene was found to be mutated in 42 samples (69%) and intragenic mutations of the NRAS gene were detected in seven samples (11%). No cell line carried mutations of both genes. Using support vector machines, we have built a classifier that differentiates between melanoma cell lines based on BRAF mutation status. As few as 83 genes are able to discriminate between BRAF mutant and BRAF wild-type samples with clear separation observed using hierarchical clustering. Multidimensional scaling was used to visualize the relationship between a BRAF mutation signature and that of a generalized mitogen-activated protein kinase (MAPK) activation (either BRAF or NRAS mutation) in the context of the discriminating gene list. We observed that samples carrying NRAS mutations lie somewhere between those with or without BRAF mutations. These observations suggest that there are gene-specific mutation signals in addition to a common MAPK activation that result from the pleiotropic effects of either BRAF or NRAS on other signaling pathways, leading to measurably different transcriptional changes.

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133 citations in Scopus
123 citations in Web of Science®
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ID Code: 45825
Item Type: Journal Article
Refereed: Yes
Keywords: Amino Acid Substitution, Humans, Melanoma/genetics/ metabolism, Mutation, Oligonucleotide Array Sequence Analysis, Proto-Oncogene Proteins B-raf, Proto-Oncogene Proteins c-raf/ genetics, ras Proteins/genetics
DOI: 10.1038/sj.onc.1207563
ISSN: 0950-9232
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Divisions: Past > Schools > Cell & Molecular Biosciences
Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 15 Sep 2011 06:00
Last Modified: 15 Sep 2011 06:00

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