To better characterize the evolution of intra-patient heterogeneity under different treatment regimens, we performed exome sequencing on multiple samples from 3 stage IV melanoma patients (cohort 1) who each received a different therapy (BRAF inhibitor (patient 1), MEK inhibitor (patient 3) or multi-receptor tyrosine kinase (patient 2)) but progressed quickly under treatment. The gene discussed is BRAF; the disease is melanoma.