@entity99 is a rare and @entity146 . Pathogenic driver mutations are largely unknown. We present the case of a @entity1 with recurrent @entity99 , who initially showed good response to @entity2240 , followed by progression. Using comprehensive molecular techniques, we explored the potential mechanisms of resistance. By low-read-depth whole-genome sequencing, the comparison of copy number aberrations (CNAs) of the @entity5 to the skin metastatic lesion that developed after progression on @entity2240 , revealed high-level amplification of the 4q11-q13.1 region (containing @entity2467 , @entity675 and @entity319 genes) that was sustained in both lesions. Whole exome sequencing on the germline, primary and @entity3 DNAs, resulted in 27 confirmed mutations, 19 of which (including @entity876 mutation) presented in both primary and metastatic lesions. One mutation, @entity68789 frameshift deletion, was detected only in the @entity5 . In contrast, seven other mutations, including @entity7985 ( @entity7985 ) @entity57215 mutation, were found only in the @entity3 , indicating selection of cells with the resistant genotype under @entity2240 pressure. Our study supports the notion that @entity7985 - @entity57215 mutation may confer @entity319 -independent signaling and may thus cause resistance against @entity7 (R)-directed therapies. This case illustrates also the advantages of using next-generation technologies in identifying individualized targeted therapy.

@entity7985 ( @entity7985 ) XXXX mutation is counterselected under targeted therapy in a @entity1 with @entity99 .

@entity1 :: ('9606', 'Species') :: ['patient'] @entity675 :: ('5156', 'Gene') :: ['PDGFRA'] @entity2240 :: ('MESH:C473478', 'Chemical') :: ['sunitinib'] @entity146 :: ('MESH:D001523', 'Disease') :: ['aggressive vascular neoplasm'] @entity5 :: ('MESH:D009369', 'Disease') :: ['primary tumor'] @entity7 :: ('7422', 'Gene') :: ['VEGF'] @entity68789 :: ('55422', 'Gene') :: ['ZNF331'] @entity7985 :: ('5335', 'Gene') :: ['phospholipase C-gamma1', 'PLCG1'] @entity876 :: ('7157', 'Gene') :: ['TP53'] @entity319 :: ('3791', 'Gene') :: ['VEGFR2'] @entity57215 :: ('p|SUB|R|707|Q', 'ProteinMutation') :: ['R707Q'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastatic tumor'] @entity2467 :: ('3815', 'Gene') :: ['KIT'] @entity99 :: ('MESH:D056486', 'Disease') :: ['Hepatic angiosarcoma', 'hepatic angiosarcoma']
@entity57215 :: (p|SUB|R|707|Q,ProteinMutation) :: ['R707Q']
