A targeted genomic alteration analysis predicts survival of melanoma patients under BRAF inhibitors.

Several mechanisms have been described to elucidate the emergence of resistance to MAPK inhibitors in melanoma and there is a crucial need for biomarkers to identify patients who are likely to achieve a better and long-lasting response to BRAF inhibitors therapy. In this study, we developed a targeted approach combining both mRNA and DNA alterations analysis focusing on relevant gene alterations involved in acquired BRAF inhibitor resistance. We collected baseline tumor samples from 64 melanoma patients at BRAF inhibitor treatment initiation and showed that the presence, prior to treatment, of mRNA over-expression of genes' subset was significantly associated with improved progression free survival and overall survival. The presence of DNA alterations was in favor of better overall survival. The genomic analysis of relapsed-matched tumor samples from 20 patients allowed us to uncover the largest landscape of resistance mechanisms reported to date as at least one resistance mechanism was identified for each patient studied. Alterations in

Déclaration de conflit d'intérêts

CONFLICTS OF INTEREST BL, JD, CRdM, LG, FJ, AS, MPP, IC, OM, JC, JPF and ND have no conflicts of interest to declare. MB declares a consulting role for Histalim, Bristol-Myers Squibb, and Innate Pharma. SD is a principal investigator in studies conducted by Roche-Genentech and Novartis. CL declares honoraria from Roche, advisory roles at Roche, GSK, Novartis, BMS, MSD, and Amgen and travel accommodation provided by Roche. SM declares a consulting role at Roche, Janssen and Novartis.