PMID- 22791410
OWN - NLM
STAT- MEDLINE
DCOM- 20140326
LR  - 20161125
IS  - 1097-0347 (Electronic)
IS  - 1043-3074 (Linking)
VI  - 35
IP  - 8
DP  - 2013 Aug
TI  - Sinonasal mucosal melanoma: Molecular profile and therapeutic implications from a 
      series of 32 cases.
PG  - 1066-77
LID - 10.1002/hed.23079 [doi]
AB  - 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.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Turri-Zanoni, Mario
AU  - Turri-Zanoni M
AD  - Department of Otorhinolaryngology, University of Brescia, Brescia, Italy.
FAU - Medicina, Daniela
AU  - Medicina D
FAU - Lombardi, Davide
AU  - Lombardi D
FAU - Ungari, Marco
AU  - Ungari M
FAU - Balzarini, Piera
AU  - Balzarini P
FAU - Rossini, Cristina
AU  - Rossini C
FAU - Pellegrini, Wilma
AU  - Pellegrini W
FAU - Battaglia, Paolo
AU  - Battaglia P
FAU - Capella, Carlo
AU  - Capella C
FAU - Castelnuovo, Paolo
AU  - Castelnuovo P
FAU - Palmedo, Gabriele
AU  - Palmedo G
FAU - Facchetti, Fabio
AU  - Facchetti F
FAU - Kutzner, Heinz
AU  - Kutzner H
FAU - Nicolai, Piero
AU  - Nicolai P
FAU - Vermi, William
AU  - Vermi W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120712
PL  - United States
TA  - Head Neck
JT  - Head & neck
JID - 8902541
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (RREB1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 136601-57-5 (Cyclin D1)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cohort Studies
MH  - Cyclin D1/physiology
MH  - DNA-Binding Proteins/physiology
MH  - Female
MH  - Genes, myb/physiology
MH  - Genes, p16/physiology
MH  - Genes, ras/physiology
MH  - Humans
MH  - Male
MH  - Melanoma/*genetics/pathology/*therapy
MH  - Middle Aged
MH  - Mutation/physiology
MH  - *Nasal Mucosa
MH  - PTEN Phosphohydrolase/physiology
MH  - Paranasal Sinus Neoplasms/*genetics/pathology/*therapy
MH  - Proto-Oncogene Proteins B-raf/physiology
MH  - Proto-Oncogene Proteins c-kit/physiology
MH  - Transcription Factors/physiology
OTO - NOTNLM
OT  - KIT
OT  - NRAS
OT  - PI3K/Akt pathway
OT  - RAS-MAPK pathway
OT  - sinonasal melanoma
EDAT- 2012/07/14 06:00
MHDA- 2014/03/29 06:00
CRDT- 2012/07/14 06:00
PHST- 2012/05/04 00:00 [accepted]
PHST- 2012/07/14 06:00 [entrez]
PHST- 2012/07/14 06:00 [pubmed]
PHST- 2014/03/29 06:00 [medline]
AID - 10.1002/hed.23079 [doi]
PST - ppublish
SO  - Head Neck. 2013 Aug;35(8):1066-77. doi: 10.1002/hed.23079. Epub 2012 Jul 12.