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Int J Cancer. 2016 May 1;138(9):2257-62. doi: 10.1002/ijc.29970. Epub 2016 Jan 11.

MAP kinase pathway gene copy alterations in NRAS/BRAF wild-type advanced melanoma.

Author information

1
Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
2
Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
3
Institute of Pathology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.

Abstract

Recent therapeutic advances have improved melanoma patientś clinical outcome. Novel therapeutics targeting BRAF, NRAS and cKit mutant melanomas are widely used in clinical practice. However therapeutic options in NRAS(wild-type) /BRAF(wild-type) /cKit(wild-type) melanoma patients are limited. Our study shows that gene copy numbers of members of the MAPK signaling pathway vary in different melanoma subgroups. NRAS(wild-type) /BRAF(wild-type) melanoma metastases are characterized by significant gains of MAP2K1 (MEK1) and MAPK3 (ERK1) gene loci. These additional gene copies could lead to an activation of the MAPK signaling pathway via a gene-dosage effect. Our results suggest that downstream analyses of the pMEK and pERK expression status in NRAS(wild-type) /BRAF(wild-type) melanoma patients identify patients that could benefit from targeted therapies with MEK and ERK inhibitors.

KEYWORDS:

BRAF; ERK; MEK; NRAS; melanoma

PMID:
26684394
DOI:
10.1002/ijc.29970
[Indexed for MEDLINE]
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