 we sequenced 8 melanoma exomes to identify novel somatic mutations in metastatic melanoma . 
 focusing on the map3k family , we found that 24% of melanoma cell lines have mutations in the protein - coding regions of either map3k5 or map3k9 . 
 structural modelling predicts that mutations in the kinase domain may affect the activity and regulation of map3k5/9 protein kinases . 
 the position of the mutations and loss of heterozygosity of map3k5 and map3k9 in 85% and 67% of melanoma samples , respectively , together suggest that the mutations are likely inactivating . in vitro kinase assay 
 shows reduction in kinase activity in map3k5 i780f and map3k9 w333x mutants . 
 overexpression of map3k5 or map3k9 mutant in hek293 t cells reduces phosphorylation of downstream map kinases . 
 attenuation of map3k9 function in melanoma cells using sirna leads to increased cell viability after temozolomide treatment , suggesting that decreased map3k pathway activity can lead to chemoresistance in melanoma . 
Supplementary Material