Sinonasal mucosal melanoma: Molecular profile and therapeutic implications from a series of 32 cases. Issue 8 (12th July 2012)

• Record Type: Journal Article
• Authors: Turri–Zanoni, Mario; Medicina, Daniela; Lombardi, Davide; Ungari, Marco; Balzarini, Piera; Rossini, Cristina; Pellegrini, Wilma; Battaglia, Paolo; Capella, Carlo; Castelnuovo, Paolo; Palmedo, Gabriele; Facchetti, Fabio; Kutzner, Heinz; Nicolai, Piero; Vermi, William
• Is Part Of: Head & neck. Volume 35:Issue 8(2013:Aug.)
• Page Start: 1066
• Page End: 1077
• Publication Date: 2012-07-12
• Subjects: Head -- Diseases -- Periodicals; Neck -- Diseases -- Periodicals; Head -- Periodicals; Neck -- Periodicals; Face -- Periodicals; 617.51059
• DOI: 10.1002/hed.23079
• Languages: English
• ISSNs: 1043-3074

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="abs1-1" sec-type="section"> <title>Background</title> <p>Primary sinonasal mucosal melanomas are aggressive tumors with a poor clinical control by current treatments, raising the urgent need of novel strategies.</p> </sec> <sec id="abs1-2" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="abs1-3" sec-type="section"> <title>Results</title> <p>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 <italic>RREB1</italic> (100%) and loss of <italic>MYB</italic> (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.</p> </sec> <sec id="abs1-4" sec-type="section"> <title>Conclusions</title> <p>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. Head Neck, 2013</p> </sec> </abstract>