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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Variations of BRAF mutant allele percentage in melanomas

Authors: Zofia Hélias-Rodzewicz, Elisa Funck-Brentano, Laure Baudoux, Chan Kwon Jung, Ute Zimmermann, Cristi Marin, Thierry Clerici, Catherine Le Gall, Frédérique Peschaud, Valérie Taly, Philippe Saiag, Jean-François Emile

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

BRAF mutations are present in 40 % of human skin melanomas. Mutated tumors with an increased percentage of BRAF mutant alleles (BRAF-M%) may have a better response to RAF/MEK inhibitors. We evaluated the BRAF-M% in melanomas, and the genetic causes of its variation.

Methods

BRAF-M% was quantified by pyrosequencing, real-time PCR (rtPCR) and/or picoliter-droplet PCR (dPCR). BRAF mutant expression was detected by immunohistochemistry. Chromosomal alterations were analyzed with fluorescence in situ hybridization (FISH), and single nucleotide polymorphism (SNP) arrays.

Results

BRAF-M% quantification obtained with pyrosequencing was highly correlated (R = 0.94) with rtPCR, and with dPCR. BRAF-M% quantified from DNA and RNA were also highly correlated (R = 0.98). Among 368 samples with >80 % tumor cells, 38.6 % had a BRAF V600E mutation. Only 66.2 % cases were heterozygous (BRAF-M% 30 to 60 %). Increased BRAF-M% (>60 %) was observed in 19 % of cases. FISH showed a polysomy of chromosome 7 in 13.6 %, 35.3 % and 54.5 % of BRAF wild-type, heterozygous and non-heterozygous BRAF-mutated samples, respectively (P < 0.005). Amplification (5.6 %) and loss (3.2 %) of BRAF locus were rare. By contrast, chromosome 7 was disomic in 27/27 BRAF-mutated nevi.

Conclusions

BRAF-M% is heterogeneous and frequently increased in BRAF-mutant melanomas. Aneuploidy of chromosome 7 is more frequent in BRAF mutant melanomas, specifically in those with high BRAF-M%.
Appendix
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Metadata
Title
Variations of BRAF mutant allele percentage in melanomas
Authors
Zofia Hélias-Rodzewicz
Elisa Funck-Brentano
Laure Baudoux
Chan Kwon Jung
Ute Zimmermann
Cristi Marin
Thierry Clerici
Catherine Le Gall
Frédérique Peschaud
Valérie Taly
Philippe Saiag
Jean-François Emile
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1515-3

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