Microarray expression profiling in melanoma reveals a BRAF mutation signature

Research output: Contribution to journalArticle

Abstract

We have used microarray gene expression pro. ling 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.

Details

Authors
  • S Pavey
  • Peter Johansson
  • L Packer
  • J Taylor
  • M Stark
  • PM Pollock
  • GJ Walker
  • GM Boyle
  • U Harper
  • SJ Cozzi
  • K Hansen
  • L Yudt
  • C Schmidt
  • P Hersey
  • KAO Ellem
  • MGE O'Rourke
  • PG Parsons
  • P Meltzer
  • Markus Ringnér
  • NK Hayward
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • mitogenactivated protein kinase, microarray, BRAF, melanoma, mutation
Original languageEnglish
Pages (from-to)4060-4067
JournalOncogene
Volume23
Issue number23
Publication statusPublished - 2004
Publication categoryResearch
Peer-reviewedYes