BRAF, NRAS, KIT, TERT, GNAQ/GNA11 mutation profile analysis of head and neck mucosal melanomas: a study of 42 cases

Pathology. 2017 Jan;49(1):55-61. doi: 10.1016/j.pathol.2016.09.065. Epub 2016 Nov 30.

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.

Keywords: BRAF; GNAQ/GNA11; KIT; Mucosal melanoma; NRAS; TERT; head and neck; mutation; oral melanoma; sinonasal melanoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • DNA Mutational Analysis / methods
  • Female
  • GTP Phosphohydrolases / genetics
  • GTP-Binding Protein alpha Subunits / genetics
  • Genetic Predisposition to Disease*
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Male
  • Melanoma / genetics*
  • Membrane Proteins / genetics
  • Middle Aged
  • Mutation / genetics*
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-kit / genetics
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / genetics*
  • Telomerase / genetics

Substances

  • GNA11 protein, human
  • GTP-Binding Protein alpha Subunits
  • Membrane Proteins
  • Proto-Oncogene Proteins c-kit
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • TERT protein, human
  • Telomerase
  • GTP Phosphohydrolases
  • NRAS protein, human