Microarray expression profiling in melanoma reveals a BRAF mutation signature

被引:140
作者
Pavey, S
Johansson, P
Packer, L
Taylor, J
Stark, M
Pollock, PM
Walker, GJ
Boyle, GM
Harper, U
Cozzi, SJ
Hansen, K
Yudt, L
Schmidt, C
Hersey, P
Ellem, KAO
O'Rourke, MGE
Parsons, PG
Meltzer, P
Ringnér, M
Hayward, NK
机构
[1] Queensland Inst Med Res, Herston, Qld 4006, Australia
[2] Lund Univ, Dept Theoret Phys, Complex Syst Div, SE-22362 Lund, Sweden
[3] Pk Ctr Mental Hlth, Queensland Ctr Schizophrenia Res, Wacol, Qld 4076, Australia
[4] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA
[5] Univ Newcastle, Newcastle, NSW 2300, Australia
[6] Mater Misericordiae Univ Hosp, Brisbane, Qld 4101, Australia
基金
英国医学研究理事会;
关键词
BRAF; melanoma; microarray; mitogenactivated protein kinase; mutation;
D O I
10.1038/sj.onc.1207563
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:4060 / 4067
页数:8
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