title: Beyond the BRAFV600Ehotspot: biology and clinical implications of rare BRAF gene mutations in melanoma patients.
abstract: BRAF gene mutations can be found in approximately 50% of melanomas, but the most common BRAF mutation leads to substitution at residue 600 of the protein, from valine to glutamic acid. BRAFV600Eoccurs in up to 95% of all melanoma cases and can be successfully blocked by using a combination of BRAF- and MEK inhibitors. The wider availability of next-generation sequencing is revealing more non-V600 BRAF mutations, and the clinical implications of these mutations are widely unknown. In this review, we will discuss the biology of the MAPK pathway and the different types of BRAF mutations as well as their effect on MEK activation. Current literature will be reviewed including in vitro data, case reports and case series.
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.|Department of Dermatology, Medical University of Graz, Graz, Austria.
authors.forename: G
authors.identifier: http://orcid.org/0000-0002-4437-4413
authors.initials: G
authors.lastname: Richtig
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Hoeller
authors.affiliation: Institute for Pathology, Medical University of Graz, Graz, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Kashofer
authors.affiliation: Institute for Pathology, Medical University of Graz, Graz, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Aigelsreiter
authors.affiliation: Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Heinemann
authors.affiliation: Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, U.S.A.
authors.forename: L N
authors.initials: LN
authors.lastname: Kwong
authors.affiliation: Division of Oncology, Medical University of Graz, Graz, Austria.|Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, U.S.A.
authors.forename: M
authors.initials: M
authors.lastname: Pichler
authors.affiliation: Department of Dermatology, Medical University of Graz, Graz, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Richtig
mesh_terms: D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology; D008545:Melanoma / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020930:MAP Kinase Kinase Kinases; D018631:ras Proteins