Differential gene expression in melanocytic nevi with the V600E BRAF mutation.
We studied gene expression in 18 melanocytic nevi with and four nevi without the V600E mutation in the BRAF gene using HG-U133A 2.0 microarray with 22,277 transcripts. Data analysis revealed 92 genes up-regulated and 105 genes down-regulated in nevi with the mutation compared to nevi without mutation. Pathway analysis showed that differentially regulated genes mapped to 10 genetic networks. The major network included genes involved in cell death, cell cycle, and cellular growth and proliferation. Up-regulated genes in nevi with the mutation included CDKN2A, CDKN1C, and MITF; whereas down-regulated genes included those involved in apoptotic and other pathways. Principal component analysis identified 22 probe sets (20 genes) that caused separate segregation of nevi with and without mutations. In conclusion, our data showed differences in gene expression between nevi with and without the V600E BRAF mutation. Moreover, nevi with mutations showed over-expression of genes involved in melanocytic senescence and cell cycle inhibition.
Bloethner
Sandra
S
Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Snellman
Erna
E
Bermejo
Justo Lorenzo
JL
Hiripi
Eva
E
Gast
Andreas
A
Thirumaran
Ranjit K
RK
Wellenreuther
Ruth
R
Hemminki
Kari
K
Kumar
Rajiv
R
D000328:Adult; D016000:Cluster Analysis; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009508:Nevus, Pigmented / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf