title: Clinical significance of BRAF mutation status in circulating tumor DNA of metastatic melanoma patients at baseline.
abstract: Circulating tumor DNA is a promising non-invasive tool for cancer monitoring. The main objective of our work was to investigate the relationship between mutant BRAF DNA in plasma and clinical response. Thirty-eight stage IV patients with a V600 mutated BRAF melanoma were included prior to any treatment. DNA was extracted from plasma and mutant DNA was detected using the amplification-refractory mutation system method. Before the beginning of any treatment, the corresponding BRAF mutation was detected in 29 of the 38 tested plasma samples (76.3% positive per cent agreement). We observed a strong correlation between the presence of circulating mutated DNA and overall survival (OS; P=.02), and with the number of metastatic sites (P=.01). The presence of circulating mutated DNA was also strongly correlated with serum LDH activity (P<.01) and S100 protein concentration (P<.01). Finally, seven patients presented discordant BRAF status in different tumor sites. In all these patients, the test performed on ctDNA was positive, suggesting that ctDNA analysis might be less sensitive to tumor heterogeneity. Altogether, these results suggest that plasmatic mutant BRAF DNA is a prognostic factor of OS, correlated with tumor burden. In addition, it represents an interesting alternative source of DNA to detect BRAF mutations before treatment.
authors.affiliation: CRCNA, , INSERM U892, CNRS 6299, Nantes Cedex 01, France.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Knol
authors.affiliation: CRCNA, , INSERM U892, CNRS 6299, Nantes Cedex 01, France.|Laboratoire de Biochimie et Plateforme de Génétique des Cancers, CHU Hôtel-Dieu, Nantes Cedex 01, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Vallée
authors.affiliation: CRCNA, , INSERM U892, CNRS 6299, Nantes Cedex 01, France.|Laboratoire de Biochimie et Plateforme de Génétique des Cancers, CHU Hôtel-Dieu, Nantes Cedex 01, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Herbreteau
authors.affiliation: CRCNA, , INSERM U892, CNRS 6299, Nantes Cedex 01, France.|SEB-PIMESP, CHU Nantes, Nantes Cedex 01, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Nguyen
authors.affiliation: CRCNA, , INSERM U892, CNRS 6299, Nantes Cedex 01, France.|Unité de Cancéro-Dermatologie-CIC biothérapie INSERM 0503, CHU Hôtel-Dieu, Nantes Cedex 01, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Varey
authors.affiliation: SEB-PIMESP, CHU Nantes, Nantes Cedex 01, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Gaultier
authors.affiliation: CRCNA, , INSERM U892, CNRS 6299, Nantes Cedex 01, France.|Laboratoire de Biochimie et Plateforme de Génétique des Cancers, CHU Hôtel-Dieu, Nantes Cedex 01, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Théoleyre
authors.affiliation: CRCNA, , INSERM U892, CNRS 6299, Nantes Cedex 01, France.|Unité de Cancéro-Dermatologie-CIC biothérapie INSERM 0503, CHU Hôtel-Dieu, Nantes Cedex 01, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Saint-Jean
authors.affiliation: CRCNA, , INSERM U892, CNRS 6299, Nantes Cedex 01, France.|Unité de Cancéro-Dermatologie-CIC biothérapie INSERM 0503, CHU Hôtel-Dieu, Nantes Cedex 01, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Peuvrel
authors.affiliation: CRCNA, , INSERM U892, CNRS 6299, Nantes Cedex 01, France.|Unité de Cancéro-Dermatologie-CIC biothérapie INSERM 0503, CHU Hôtel-Dieu, Nantes Cedex 01, France.
authors.forename: Anabelle
authors.initials: A
authors.lastname: Brocard
authors.affiliation: CRCNA, , INSERM U892, CNRS 6299, Nantes Cedex 01, France.|Unité de Cancéro-Dermatologie-CIC biothérapie INSERM 0503, CHU Hôtel-Dieu, Nantes Cedex 01, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Quéreux
authors.affiliation: CRCNA, , INSERM U892, CNRS 6299, Nantes Cedex 01, France.|Unité de Cancéro-Dermatologie-CIC biothérapie INSERM 0503, CHU Hôtel-Dieu, Nantes Cedex 01, France.
authors.forename: Amir
authors.initials: A
authors.lastname: Khammari
authors.affiliation: CRCNA, , INSERM U892, CNRS 6299, Nantes Cedex 01, France.|Laboratoire de Biochimie et Plateforme de Génétique des Cancers, CHU Hôtel-Dieu, Nantes Cedex 01, France.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Denis
authors.affiliation: CRCNA, , INSERM U892, CNRS 6299, Nantes Cedex 01, France. brigitte.dreno@wanadoo.fr.|Unité de Cancéro-Dermatologie-CIC biothérapie INSERM 0503, CHU Hôtel-Dieu, Nantes Cedex 01, France. brigitte.dreno@wanadoo.fr.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dréno
mesh_terms: D000328:Adult; D000368:Aged; D000074141:Circulating Tumor DNA / Q000737:chemistry*; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008545:Melanoma / Q000097:blood / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D009362:Neoplasm Metastasis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D009418:S100 Proteins / Q000097:blood
chemical_list: D000074141:Circulating Tumor DNA; D009418:S100 Proteins; D007770:L-Lactate Dehydrogenase; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF mutation; metastatic melanoma; overall survival; plasma DNA