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.
Type de document :
Article dans une revue
Experimental Dermatology, Wiley, 2016, 25, pp.783 - 788. 〈10.1111/exd.13065〉
Liste complète des métadonnées

Littérature citée [22 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-01408920
Contributeur : Elizabeth Bernardo <>
Soumis le : lundi 5 décembre 2016 - 15:03:40
Dernière modification le : jeudi 5 avril 2018 - 10:36:50
Document(s) archivé(s) le : mardi 21 mars 2017 - 03:13:16

Fichier

 Accès restreint
Fichier visible le : jamais

Connectez-vous pour demander l'accès au fichier

Identifiants

Collections

Citation

Anne Knol, Audrey Vallée, Guillaume Herbreteau, Jean-Michel Nguyen, Emilie Varey, et al.. Clinical significance of BRAF mutation status in circulating tumor DNA of metastatic melanoma patients at baseline. Experimental Dermatology, Wiley, 2016, 25, pp.783 - 788. 〈10.1111/exd.13065〉. 〈inserm-01408920〉

Partager

Métriques

Consultations de la notice

90