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- Title
L576P KIT mutation in anal melanomas correlates with KIT protein expression and is sensitive to specific kinase inhibition.
- Authors
Antonescu, Cristina R.; Busam, Klaus J.; Francone, Todd D.; Wong, Grace C.; Guo, Tianhua; Agaram, Narasimhan P.; Besmer, Peter; Jungbluth, Achim; Gimbel, Mark; Chen, Chin-Tung; Veach, Darren; Clarkson, Bayard D.; Paty, Philip B.; Weiser, Martin R.
- Abstract
Activating mutations in either BRAF or NRAS are seen in a significant number of malignant melanomas, but their incidence appears to be dependent to ultraviolet light exposure. Thus, BRAF mutations have the highest incidence in non-chronic sun damaged (CSD), and are uncommon in acral, mucosal and CSD melanomas. More recently, activating KIT mutations have been described in rare cases of metastatic melanoma, without further reference to their clinical phenotypes. This finding is intriguing since KIT expression is downregulated in most melanomas progressing to more aggressive lesions. In this study, we investigated a group of anal melanomas for the presence of BRAF, NRAS, KIT and PDGFRA mutations. A heterozygous KIT exon 11 L576P substitution was identified in 3 of 20 cases tested. The 3 KIT mutation-carrying tumors were strongly immunopositive for KIT protein. No KIT mutations were identified in tumors with less than 4+ KIT immunostaining. NRAS mutation was identified in one tumor. No BRAF or PDGFRA mutations were identified in either KIT positive or negative anal melanomas. In vitro drug testing of stable transformant Ba/F3 KIT
- Publication
International Journal of Cancer, 2007, Vol 121, Issue 2, p257
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.22681