MAP2K4 and cancer: Recent large-scale genomic studies have identified oncogenic driver mutations in multiple cancers, including recurrent mutations in MAP3K1 and MAP2K4. 12–14 The MAP3K1 and MAP2K4 mutations are loss-of-function mutations, including nonsense and frame shift mutations and a missense mutation (Ser56Leu), which interferes with MAP2K4 kinase activity.12,13,15 The highest mutation frequency in these genes is found in invasive ductal breast cancers: MAP3K1 9% and MAP2K4 7%,16 followed by cancers of prostate, stomach and diffuse large B cell lymphoma16–21 (http://www.cbioportal.org).