Variation of mutant allele frequency in NRAS Q61 mutated melanomasReportar como inadecuado

Variation of mutant allele frequency in NRAS Q61 mutated melanomas - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Dermatology

, 17:9

Skin cancer


BackgroundSomatic mutations of BRAF or NRAS activating the MAP kinase cell signaling pathway are present in 70% of cutaneous melanomas. The mutant allele frequency of BRAF V600E M%BRAF was recently shown to be highly heterogeneous in melanomas. The present study focuses on the NRAS Q61 mutant allele frequency M%NRAS.

MethodsRetrospective quantitative analyze of 104 NRAS mutated melanomas was performed using pyrosequencing. Mechanisms of M%NRAS imbalance were studied by fluorescence in situ hybridization FISH and microsatellite analysis.

ResultsM%NRAS was increased in 27.9% of cases. FISH revealed that chromosome 1 instability was the predominant mechanism of M%NRAS increase, with chromosome 1 polysomy observed in 28.6% of cases and intra-tumor cellular heterogeneity with copy number variations of chromosome 1-NRAS in 23.8%. Acquired copy-neutral loss of heterozygosity LOH was less frequent 19%. However, most samples with high M%NRAS had only one copy of NRAS locus surrounding regions suggesting a WT allele loss. Clinical characteristics and survival of patients with either <60% or ≥60% of M%NRAS were not different.

ConclusionAs recently shown for M%BRAF, M%NRAS is highly heterogeneous. The clinical impacts of high M%NRAS should be investigated in a larger series of patients.

KeywordsMelanoma M%NRAS Imbalance Pyrosequencing WT allele loss AbbreviationsALFPAmplified fragment length polymorphism

DMFSDistant metastasis free survival

FISHFluorescence in situ hybridization


LOHLoss of heterozygosity

M%NRASNRAS mutant allele frequency

OSOverall survival

PFSProgression-free survival

Electronic supplementary materialThe online version of this article doi:10.1186-s12895-017-0061-x contains supplementary material, which is available to authorized users.

Download fulltext PDF

Autor: Zofia Hélias-Rodzewicz - Elisa Funck-Brentano - Nathalie Terrones - Alain Beauchet - Ute Zimmermann - Cristi Marin - Philip


Documentos relacionados