Predictive value of integrative epigenetic profiling in metastatic melanoma (MM) patients (p) treated with BRAF/MEK inhibitors (BMI) and chemotherapy (CT).

e20059 Background: The treatment of MM has evolved over the last four years to include novel treatments in addition to CT, requiring predictive markers of response. Treatment with BMI provides benefit in overall survival, although with early resistance development. The value of CT in these p is limited. Hence, the aim of this work is to perform an integrative epigenetic profiling as predictive tool of resistance to treatment in MM p treated, in one hand with BRAF/MEK inhibitors, and in the other hand, CT-based treatment. The final goal is obtain epigenetic biomarkers to optimize treatment selection and p's outcome. Additionally, we pretend to identify epigenetic biomarkers related to metastatic process. Methods: It was analyzed 35 paraffin-embebbed primary tumor tissue samples from 35 MM p, 20 of them had been treated with BMI and 15 with CT. Additionally, it was analyzed the paired metastasis tissue for a half of them to study the effect of epigenetics in metastatic process. Epigenetic screening was performed using DNA methylation array technology Infinium 450K from Illumina, following the manufacturer's instructions. Data analysis was performed using R statistics software. Results: Comparing responders and non-responders p, we obtained an epigenetic profile associated with drug resistance prediction for each treatment strategy (target therapy and CT). Regarding metastatic process, we compared primary tumor with paired metastasis identifying a set of epigenetic biomarkers candidates. In all cases, it was considered as significant those methylation changes with beta-values differences over 10% and ANOVA with p-value under 0.01. Conclusions: According our high-throughput epigenetic screening, we have been capable to discriminate in a cohort of MM p between responders and refractory tumors focusing in DNA methylation changes. Moreover, epigenetic changes are also presented as a strategy to understand better the metastasis process in this neoplasia. Hence, integrated epigenetic screening could be a useful tool to optimize treatment selection. Nevertheless, further studies are warranted to elucidate their potential role in the clinical setting.