Fig. 5

Presentation of a case study with a novel actionable mutation p.D587H (hg19 chr7:55233009G > C) in EGFR. a EGFR mutation frequencies in several cancer types were obtained from TCGA data (http://cancergenome.nih.gov) and plotted across the EGFR protein sequence. D587 (dashed red line) is located near a hotspot at G598 within domain IV. Kinase domain and domain II hotspots are also depicted. Domain structure is from Pfam [63]. b Structure of the extracellular region of EGFR depicting individual domains; I (yellow), II (orange), III (teal), and IV (silver). A view of the interaction between domains II and IV is illustrated (box). Side chain of D587 (black) and K609 (green) form an interaction (red dashed line). Hydrogen bonding (red dashed lines) between domain IV residues and domain II tyrosine residues (orange) stabilize the inactive conformation. Hotspot regions (green side chains) may be allowing for a conformation of the loop that permits interaction between D587 and K609. c HEK293 cells were transfected with EGFR, p.D587H, or p.L858R, and activity of EGFR was assayed by western blot using an anti-phosphotyrosine antibody to measure autophosphorylation