Title |
Variations of BRAF mutant allele percentage in melanomas
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Published in |
BMC Cancer, July 2015
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DOI | 10.1186/s12885-015-1515-3 |
Pubmed ID | |
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 |
Abstract |
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. 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. 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. 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%. |
X Demographics
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Unknown | 1 | 100% |
Demographic breakdown
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
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Portugal | 1 | 2% |
Unknown | 46 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 8 | 17% |
Student > Bachelor | 7 | 15% |
Researcher | 7 | 15% |
Student > Master | 6 | 13% |
Other | 4 | 9% |
Other | 7 | 15% |
Unknown | 8 | 17% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 10 | 21% |
Agricultural and Biological Sciences | 6 | 13% |
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Pharmacology, Toxicology and Pharmaceutical Science | 2 | 4% |
Other | 5 | 11% |
Unknown | 11 | 23% |