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- Title
Variation of mutant allele frequency in NRAS Q61 mutated melanomas.
- Authors
Hélias-Rodzewicz, Zofia; Funck-Brentano, Elisa; Terrones, Nathalie; Beauchet, Alain; Zimmermann, Ute; Marin, Cristi; Saiag, Philippe; Emile, Jean-François
- Abstract
<bold>Background: </bold>Somatic 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).<bold>Methods: </bold>Retrospective 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.<bold>Results: </bold>M%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.<bold>Conclusion: </bold>As 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.
- Subjects
ALLELES; CHROMOSOMES; ARTIFICIAL chromosomes; GENE frequency; GENETIC mutation; PHYSIOLOGY; CHROMOSOME abnormalities; GENES; GENETICS; HYDROLASES; MELANOMA; MEMBRANE proteins; SKIN tumors; RETROSPECTIVE studies; KAPLAN-Meier estimator
- Publication
BMC Dermatology, 2017, Vol 17, p1
- ISSN
1471-5945
- Publication type
journal article
- DOI
10.1186/s12895-017-0061-x