Microarray expression profiling in melanoma reveals a BRAF mutation signature

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 S Hansen, Laura Yudt, Chris Schmidt, Peter Hersey, Kay A O Ellem, Michael G E O'Rourke, Peter G. Parsons, Paul Meltzer, Markus Ringnér, Nicholas K. Hayward

Research output: Contribution to journalArticle

141 Scopus citations

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 BSAF 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.

Original languageEnglish (US)
Pages (from-to)4060-4067
Number of pages8
JournalOncogene
Volume23
Issue number23
DOIs
StatePublished - May 20 2004
Externally publishedYes

Keywords

  • BRAF
  • Melanoma
  • Microarray
  • Mitogen-activated protein kinase
  • Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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  • Cite this

    Pavey, S., Johansson, P., Packer, L., Taylor, J., Stark, M., Pollock, P. M., Walker, G. J., Boyle, G. M., Harper, U., Cozzi, S. J., Hansen, K. S., Yudt, L., Schmidt, C., Hersey, P., Ellem, K. A. O., O'Rourke, M. G. E., Parsons, P. G., Meltzer, P., Ringnér, M., & Hayward, N. K. (2004). Microarray expression profiling in melanoma reveals a BRAF mutation signature. Oncogene, 23(23), 4060-4067. https://doi.org/10.1038/sj.onc.1207563