Fig. 3

The nature and role of human epidermal growth factor receptor 2 (HER2) amplified (HER2A) in other cancers. a–c Tumors are grouped by HER2 amplification and mutation status. Tumors without HER2 amplification or mutation are shown in black, HER2A tumors (regardless of HER2 mutation) in red, unamplified tumors with an activating HER2 mutation (HER2MUT act) in green, and unamplified tumors with an untested or functionally inactive HER2 mutation (HER2MUT unk) in gold. a HER2 expression is consistently higher in HER2A tumors than in tumors without HER2 alteration, across all cancers (linear model with HER2 status and cancer, p = 0). Non-HER2A tumors with an activating or non-functional HER2 mutation have similar HER2 expression levels to unaltered tumors. b HER2 protein levels are higher in HER2A compared to unaltered tumors (p = 1e-104), though insignificant in lung squamous cell carcinoma (p = 0.08). HER2 protein levels in tumors with activating or non-functional HER2 mutations are similar to unaltered tumors. c Phospho-HER2 (Tyr1248) levels are significantly higher in HER2A bladder (p = 8e-12), breast (p = 3e-53), gastric (p = 1e-10), ovarian (p = 8e-20), and endometrial (p = 1e-8) tumors compared to unaltered tumors. pHER2 levels in tumors with activating or non-functional HER2 mutations are similar to unaltered tumors. d Expression of genes in a 2-Mb region around HER2, in a panel of HER2A tumors (top) and non-HER2A tumors with HER2 overexpression (o/e) (bottom). Expression is normalized per cancer to the median expression of each gene in tumors with 2 or fewer HER2 copies. The 2.5% lowest and highest values are saturated for better contrast. Genes are colored by core and broad pan-cancer HER2 amplicon