In the context of evolution from primary to metastatic disease, high depth bulk profiling of primary and matched metastatic tumours from the same patient have revealed that most distant metastases acquire genomic driver mutations not seen in the primary tumour, drawing from a wider repertoire of cancer genes than early drivers, including a number of clinically actionable mutations inactivating SWI-SNF and JAK2-STAT3 pathways36. The gene discussed is JAK2; the disease is metastatic neoplasm.