Microarray expression profiling in melanoma reveals a BRAF mutation signature View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2004-03-29

AUTHORS

Sandra Pavey, Peter Johansson, Leisl Packer, Jennifer Taylor, Mitchell Stark, Pamela M Pollock, Graeme J Walker, Glen M Boyle, Ursula Harper, Sarah-Jane Cozzi, Katherine Hansen, Laura Yudt, Chris Schmidt, Peter Hersey, Kay AO Ellem, Michael GE O'Rourke, Peter G Parsons, Paul Meltzer, Markus Ringnér, Nicholas K Hayward

ABSTRACT

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. More... »

PAGES

4060-4067

Journal

TITLE

Oncogene

ISSUE

23

VOLUME

23

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1207563

DOI

http://dx.doi.org/10.1038/sj.onc.1207563

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1036495589

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15048078


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