title: [ Spectrum of oncogene mutations is different in melanoma subtypes].
abstract: Melanoma is the most lethal malignancy of skin, which is comprised of clinically relevant molecular subsets defined by specific "driver" mutations in BRAF, NRAS, and KIT genes. Recently, the better results in melanoma treatment were obtained with the mutation-specific inhibitors that have been developed for clinical use and target only patients with particular tumor genotypes. The aim of the study was to characterize the spectrum of "driver" mutations in melanoma subtypes from 137 patients with skin melanoma and 14 patients with mucosal melanoma. In total 151 melanoma cases, the frequency of BRAF, NRAS, KIT, PDGFRA, and KRAS mutations was 55.0, 10.6, 4.0, 0.7, and 0.7%, respectively. BRAF mutations were found in 69% of cutaneous melanoma without UV exposure and in 43% of cutaneous melanoma with chronic UV exposure (p=0.045), rarely in acral and mucosal melanomas. Most of melanomas containing BRAF mutations, V600E (92%) and V600K (6.0%) were potentially sensitive to inhibitors vemurafenib and dabrafenib. NRAS mutations were more common in cutaneous melanoma with chronic UV exposure (26.0%), in acral and mucosal melanomas; the dominant mutations being Q61R/K/L (87.5%). KIT mutations were found in cutaneous melanoma with chronic UV exposure (8.7%) and mucosal one (28.6%), but not in acral melanoma. Most of KIT mutations were identified in exon 11; these tumors being sensitive to tyrosine kinase inhibitors. This is the first monitoring of BRAF, NRAS, KIT, PDGFRA, and KRAS hotspot mutations in different subtypes of melanoma for Russian population. On the base of data obtained, one can suppose that at the molecular level melanomas are heterogeneous tumors that should be tested for "driver" mutations in the each case for evaluation of the potential sensitivity to target therapy. The obtained results were used for treatment of melanoma patients.
authors.affiliation: Blokhin Russian Cancer Research Center, Ministry of Healthcare of the Russian Federation, Moscow, 115478 Russia.|nnmazurenko@mail.ru.
authors.forename: N N
authors.initials: NN
authors.lastname: Mazurenko
authors.affiliation: Blokhin Russian Cancer Research Center, Ministry of Healthcare of the Russian Federation, Moscow, 115478 Russia.
authors.forename: I V
authors.initials: IV
authors.lastname: Tsyganova
authors.affiliation: Blokhin Russian Cancer Research Center, Ministry of Healthcare of the Russian Federation, Moscow, 115478 Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Lushnikova
authors.affiliation: Blokhin Russian Cancer Research Center, Ministry of Healthcare of the Russian Federation, Moscow, 115478 Russia.
authors.forename: D A
authors.initials: DA
authors.lastname: Ponkratova
authors.affiliation: Blokhin Russian Cancer Research Center, Ministry of Healthcare of the Russian Federation, Moscow, 115478 Russia.
authors.forename: O A
authors.initials: OA
authors.lastname: Anurova
authors.affiliation: Blokhin Russian Cancer Research Center, Ministry of Healthcare of the Russian Federation, Moscow, 115478 Russia.
authors.forename: E A
authors.initials: EA
authors.lastname: Cheremushkin
authors.affiliation: Blokhin Russian Cancer Research Center, Ministry of Healthcare of the Russian Federation, Moscow, 115478 Russia.
authors.forename: I N
authors.initials: IN
authors.lastname: Mikhailova
authors.affiliation: Blokhin Russian Cancer Research Center, Ministry of Healthcare of the Russian Federation, Moscow, 115478 Russia.
authors.forename: L V
authors.initials: LV
authors.lastname: Demidov
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: BRAF; DNA sequencing; KIT; KRAS; NRAS; PDGFRA; acral melanoma; amelanotic melanoma; cutaneous melanoma; melanoma; mucosal melanoma; mutations; nevoid; nodal melanoma; oncogenes