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Microarray expression profiling in melanoma reveals a BRAF mutation signature

Pavey, S; Johansson, Peter LU ; Packer, L; Taylor, J; Stark, M; Pollock, PM; Walker, GJ; Boyle, GM; Harper, U and Cozzi, SJ, et al. (2004) In Oncogene 23(23). p.4060-4067
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... (More)
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. (Less)
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publication status
published
subject
keywords
mitogenactivated protein kinase, microarray, BRAF, melanoma, mutation
in
Oncogene
volume
23
issue
23
pages
4060 - 4067
publisher
Nature Publishing Group
external identifiers
  • wos:000221520200003
  • pmid:15048078
  • scopus:2942533921
ISSN
1476-5594
DOI
10.1038/sj.onc.1207563
language
English
LU publication?
yes
id
53282e13-e08e-4d31-b65d-31230f2a663c (old id 277176)
date added to LUP
2007-10-29 14:49:40
date last changed
2017-11-26 03:14:43
@article{53282e13-e08e-4d31-b65d-31230f2a663c,
  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.},
  author       = {Pavey, S and Johansson, Peter and Packer, L and Taylor, J and Stark, M and Pollock, PM and Walker, GJ and Boyle, GM and Harper, U and Cozzi, SJ and Hansen, K and Yudt, L and Schmidt, C and Hersey, P and Ellem, KAO and O'Rourke, MGE and Parsons, PG and Meltzer, P and Ringnér, Markus and Hayward, NK},
  issn         = {1476-5594},
  keyword      = {mitogenactivated protein kinase,microarray,BRAF,melanoma,mutation},
  language     = {eng},
  number       = {23},
  pages        = {4060--4067},
  publisher    = {Nature Publishing Group},
  series       = {Oncogene},
  title        = {Microarray expression profiling in melanoma reveals a BRAF mutation signature},
  url          = {http://dx.doi.org/10.1038/sj.onc.1207563},
  volume       = {23},
  year         = {2004},
}