title: The immune-related role of BRAF in melanoma.
abstract: BACKGROUND
  The existence of a dichotomy between immunologically active and quiescent tumor phenotypes has been recently recognized in several types of cancer. The activation of a Th1 type of immune signature has been shown to confer better prognosis and likelihood to respond to immunotherapy. However, whether such dichotomy depends on the genetic make-up of individual cancers is not known yet. BRAF and NRAS mutations are commonly acquired during melanoma progression. Here we explored the role of BRAF and NRAS mutations in influencing the immune phenotype based on a classification previously identified by our group.
  
  
  METHODS
  One-hundred-thirteen melanoma metastases underwent microarray analysis and BRAF and NRAS genotyping. Allele-specific PCR was also performed in order to exclude low-frequency mutations.
  
  
  RESULTS
  Comparison between BRAF and NRAS mutant versus wild type samples identified mostly constituents or regulators of MAPK and related pathways. When testing gene lists discriminative of BRAF, NRAS and MAPK alterations, we found that 112 BRAF-specific transcripts were able to distinguish the two immune-related phenotypes already described in melanoma, with the poor phenotype associated mostly with BRAF mutation. Noteworthy, such association was stronger in samples displaying low BRAF mRNA expression. However, when testing NRAS mutations, we were not able to find the same association.
  
  
  CONCLUSIONS
  This study suggests that BRAF mutation-related specific transcripts associate with a poor phenotype in melanoma and provide a nest for further investigation.
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD 20892, USA; Department of Genetic Medicine, Weill Cornell Medical College in Qatar, PO Box 24144, Doha, Qatar; Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar. Electronic address: stomei@sidra.org.
authors.forename: Sara
authors.initials: S
authors.lastname: Tomei
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD 20892, USA; Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar.
authors.forename: Davide
authors.initials: D
authors.lastname: Bedognetti
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Valeria
authors.initials: V
authors.lastname: De Giorgi
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD 20892, USA; Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Sommariva
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Civini
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry, Biocenter, University of Wuerzburg, Wuerzburg 97074, Germany; Genelux Corporation, San Diego Science Center, San Diego 92109, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Reinboth
authors.affiliation: Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar.
authors.forename: Muna
authors.initials: M
authors.lastname: Al Hashmi
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD 20892, USA; Center of Excellence for Biomedical Research (CEBR), University of Genoa, Italy.
authors.forename: Maria Libera
authors.initials: ML
authors.lastname: Ascierto
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Qiuzhen
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Biology, Northern Michigan University, Marquette, MI, USA.
authors.forename: Ben D
authors.initials: BD
authors.lastname: Ayotte
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College in Qatar, PO Box 24144, Doha, Qatar.
authors.forename: Andrea
authors.initials: A
authors.lastname: Worschech
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD 20892, USA; Institute of Infectious and Tropical Diseases, University of Milan, L. Sacco Hospital, Milan, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Uccellini
authors.affiliation: Istituto Nazionale Tumori Fondazione "G. Pascale", Via G. Semmola, Naples, Italy.
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Ascierto
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: David
authors.initials: D
authors.lastname: Stroncek
authors.affiliation: Institute of Biomolecular Chemistry, National Research Council, Sassari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College in Qatar, PO Box 24144, Doha, Qatar.
authors.forename: Lotfi
authors.initials: L
authors.lastname: Chouchane
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD 20892, USA; Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar.
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.affiliation: Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and Trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD 20892, USA; Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar.
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
mesh_terms: D045744:Cell Line, Tumor; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D008565:Membrane Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
keywords: BRAF; Immune phenotype; Melanoma; NRAS