title: BRAF, NRAS, KIT, TERT, GNAQ/GNA11 mutation profile analysis of head and neck mucosal melanomas: a study of 42 cases.
abstract: Head and neck mucosal melanoma (HNMuM), which occurs mostly in the sinonasal and oral cavity, constitutes less than 1% of all malignant melanomas. Treatment options fail to improve the prognosis of this aggressive tumour that has low overall survival rates. Thus, development of new targeted therapies is essential. Unfortunately, limited data exist regarding their molecular profile. BRAF, NRAS, KIT, TERT and GNAQ/GNA11 oncogene mutations were investigated in 42 HNMuMs (28 sinonasal, 13 oral, 1 nasopharyngeal). Mutation rates were as follows: BRAF (4.8%), NRAS (4.8%), KIT (9.5%), TERT (7.5%), GNAQ/GNA11 (0%). Among 11 cases that harboured mutations (26%), 10 (91%) were located in sinonasal and one (9%) in the oral cavity. The literature was reviewed with comparison of frequencies based on the gathered data. NRAS and TERT promoter mutation rates were significantly higher in sinonasal than in oral location (p<0.05). Our results indicated that BRAF, NRAS, KIT, TERT and GNAQ/GNA11 gene mutations occur at low frequencies in HNMuMs, and subgroups (oral versus sinonasal) differ in their molecular profile. Low rates of aforementioned mutations and activation of oncogenes by pathways other than sun exposure support the distinctive nature of HNMuMs with regard to their cutaneous counterparts.
authors.affiliation: Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. Electronic address: suleozturksari@gmail.com.
authors.forename: Şule
authors.initials: Ş
authors.lastname: Öztürk Sari
authors.affiliation: Department of Pathology, Haydarpaşa Training Hospital, Gülhane Military Medical Academy, Istanbul, Turkey.
authors.forename: İsmaİl
authors.initials: İ
authors.lastname: Yilmaz
authors.affiliation: Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Orhun Çiğ
authors.initials: OÇ
authors.lastname: Taşkin
authors.affiliation: Department of Pathology, Haydarpaşa Training Hospital, Gülhane Military Medical Academy, Istanbul, Turkey.
authors.forename: Gİzem
authors.initials: G
authors.lastname: Narli
authors.affiliation: Department of Medical Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey.
authors.forename: Fatma
authors.initials: F
authors.lastname: Şen
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Şenol
authors.initials: Ş
authors.lastname: Çomoğlu
authors.affiliation: Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Pinar
authors.initials: P
authors.lastname: Firat
authors.affiliation: Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Bİlge
authors.initials: B
authors.lastname: Bİlgİç
authors.affiliation: Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Dİlek
authors.initials: D
authors.lastname: Yilmazbayhan
authors.affiliation: Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Yasemİn
authors.initials: Y
authors.lastname: Özlük
authors.affiliation: Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Nesİmİ
authors.initials: N
authors.lastname: Büyükbabanİ
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012878:Skin Neoplasms / Q000175:diagnosis / Q000235:genetics*; D019098:Telomerase / Q000235:genetics
chemical_list: C554062:GNA11 protein, human; D044385:GTP-Binding Protein alpha Subunits; D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C509186:TERT protein, human; D019098:Telomerase; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
keywords: BRAF; GNAQ/GNA11; KIT; Mucosal melanoma; NRAS; TERT; head and neck; mutation; oral melanoma; sinonasal melanoma