Sinonasal mucosal melanoma: molecular profile and therapeutic implications from a series of 32 cases
| Autor: | Mario Turri-Zanoni, Carlo Capella, Heinz Kutzner, Cristina Rossini, Gabriele Palmedo, Davide Lombardi, Daniela Medicina, Marco Ungari, Fabio Facchetti, Paolo Battaglia, Paolo Castelnuovo, Piera Balzarini, Piero Nicolai, William Vermi, Wilma Pellegrini |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Proto-Oncogene Proteins B-raf Neuroblastoma RAS viral oncogene homolog Pathology medicine.medical_specialty Genes myb NRAS sinonasal melanoma medicine.disease_cause Cohort Studies medicine Humans PTEN Cyclin D1 Melanoma Protein kinase B PI3K/AKT/mTOR pathway Aged Aged 80 and over KIT NRAS PI3K/Akt pathway RAS-MAPK pathway sinonasal melanoma Mutation medicine.diagnostic_test biology business.industry RAS-MAPK pathway Genes p16 PTEN Phosphohydrolase Mucosal melanoma KIT Middle Aged medicine.disease DNA-Binding Proteins Nasal Mucosa Proto-Oncogene Proteins c-kit Genes ras Otorhinolaryngology PI3K/Akt pathway biology.protein Immunohistochemistry Female business Paranasal Sinus Neoplasms Transcription Factors Fluorescence in situ hybridization |
| ISSN: | 1066-1077 |
| Popis: | 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. V C 2012 Wiley Periodicals, Inc. Head Neck 35: 1066-1077, 2013 |
| Databáze: | OpenAIRE |
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