Sinonasal mucosal melanoma: Molecular profile and therapeutic implications from a series of 32 cases

Head Neck. 2013 Aug;35(8):1066-77. doi: 10.1002/hed.23079. Epub 2012 Jul 12.


Background: Primary sinonasal mucosal melanomas are aggressive tumors with a poor clinical control by current treatments, raising the urgent need of novel strategies.

Methods: By fluorescence in situ hybridization (FISH), direct sequencing, and immunohistochemistry, we investigate the spectrum of molecular abnormalities in a cohort of 32 cases of primary sinonasal mucosal melanomas.

Results: We found that all primary sinonasal mucosal melanomas lack BRAF V600E mutation; in addition, they are characterized by somatic mutations of NRAS (22%) and KIT (12.5%), together with amplification of RREB1 (100%) and loss of MYB (76%). The large majority of cases showed KIT protein expression (96.9%). Among tumor suppressor genes, primary sinonasal mucosal melanomas showed loss of PTEN (48.1%) and p16/INK4a (55.2%). All tested cases showed expression of pAkt and pErk, suggesting a combined activation of PI3K/Akt and RAS-mitogen-activated protein kinase (MAPK) pathways.

Conclusions: This molecular fingerprint strongly argues against the clinical efficacy of BRAF-inhibitors, but could candidate primary sinonasal mucosal melanomas to therapeutic strategies targeting RAS and KIT mutations or inhibiting PI3K-Akt-mTOR pathway.

Keywords: KIT; NRAS; PI3K/Akt pathway; RAS-MAPK pathway; sinonasal melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Cyclin D1 / physiology
  • DNA-Binding Proteins / physiology
  • Female
  • Genes, myb / physiology
  • Genes, p16 / physiology
  • Genes, ras / physiology
  • Humans
  • Male
  • Melanoma / genetics*
  • Melanoma / pathology
  • Melanoma / therapy*
  • Middle Aged
  • Mutation / physiology
  • Nasal Mucosa*
  • PTEN Phosphohydrolase / physiology
  • Paranasal Sinus Neoplasms / genetics*
  • Paranasal Sinus Neoplasms / pathology
  • Paranasal Sinus Neoplasms / therapy*
  • Proto-Oncogene Proteins B-raf / physiology
  • Proto-Oncogene Proteins c-kit / physiology
  • Transcription Factors / physiology


  • DNA-Binding Proteins
  • RREB1 protein, human
  • Transcription Factors
  • Cyclin D1
  • Proto-Oncogene Proteins c-kit
  • Proto-Oncogene Proteins B-raf
  • PTEN Phosphohydrolase
  • PTEN protein, human