Fig. 4

Details of ERBB2 alterations and a case of remarkable response to anti-HER2 therapy in the ERBB2 cluster. a Mutations of ERBB2 identified in 207 Japanese GCs are aligned to the protein domain. Patient samples are further plotted by mutation status. b Abdominal enhanced CT before trastuzumab therapy (upper panel) demonstrated extensive metastases in abdominal (arrow head) and paraaortic (arrow) lymph nodes. All the metastatic lymph nodes were remarkably reduced in size after trastuzumab therapy (lower panel). c Abdominal lymph nodes were reduced in size, and paraaortic lymphadenectomy was performed (upper panel). Histological examination revealed no viable tumor cells in the abdominal and paraaortic lymph nodes (lower panel, hematoxylin and eosin, original magnification × 40). d Genomic sequencing in biopsy specimen obtained before treatment (left panel, hematoxylin and eosin; right panel, anti-HER2 antibody) identified ERBB2 and ZNF217 amplification and TP53 mutation. However, concomitant alterations in the ERBB2 downstream pathway were not observed in the tumor of this patient