title: Gene expression signature associated with BRAF mutations in human primary cutaneous melanomas.
abstract: With the aim to correlate BRAF mutation status with gene expression in human primary cutaneous melanomas, and thus to get more insight on the consequences of BRAF mutation on cell biology, we analyzed all expression data obtained in melanomas from which DNA was extracted from the same tissue slides that were used for the expression study. A cohort of 69 frozen primary melanoma whose oligonucleotide micro-array expression data were available, were genotyped for BRAF and NRAS genes. The expression data from these melanomas were re-analyzed according to BRAF mutational status. A set of 250 probes representing 209 genes that were significantly (raw P< or =0.001) associated with BRAF mutation status was identified and 17 of these were previously shown to be implicated in cutaneous melanoma progression or pigmentation pathway-associated genes driven by the microphthalmia transcription factor (MITF). The list of 34 top probes contained no more than 1% of false discoveries with a probability of 0.95. Among the genes that differentiated most strongly between BRAF mutated and non-mutated melanomas, there were those involved in melanoma immune response such as MAGE-D2, CD63, and HSP70. These findings support the immunogenicity of BRAF(V600E), eliciting patients T-cell responses in various in vitro assays. The genes whose expression is associated with BRAF mutations are not simply restricted to the MAPK/ERK signaling but also converge to enhanced immune responsiveness, cell motility and melanosomes processing involved in the adaptative UV response.
authors.affiliation: Service de Génétique & CNRS FRE 2939, Institut Gustave Roussy, Villejuif, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Kannengiesser
authors.forename: Alain
authors.initials: A
authors.lastname: Spatz
authors.forename: Stefan
authors.initials: S
authors.lastname: Michiels
authors.forename: Alain
authors.initials: A
authors.lastname: Eychène
authors.forename: Philippe
authors.initials: P
authors.lastname: Dessen
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lazar
authors.forename: Véronique
authors.initials: V
authors.lastname: Winnepenninckx
authors.forename: Fabienne
authors.initials: F
authors.lastname: Lesueur
authors.forename: Sabine
authors.initials: S
authors.lastname: Druillennec
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
authors.forename: Joost J
authors.initials: JJ
authors.lastname: van den Oord
authors.forename: Alain
authors.initials: A
authors.lastname: Sarasin
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bressac-de Paillerets
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002465:Cell Movement / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D015342:DNA Probes / Q000592:standards; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007109:Immunity / Q000235:genetics; D007223:Infant; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D020460:Melanosomes; D008875:Middle Aged; D020125:Mutation, Missense; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D014466:Ultraviolet Rays; D055815:Young Adult
chemical_list: D015342:DNA Probes; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf