Epidermal growth factor receptor exon 19 deletion mutation (EGFR exon 19 deletion)

The epidermal growth factor receptor exon 19 deletion mutation refers to a group of in-frame deletions within the region encoded by exon 19 of the EGFR gene. These deletions most commonly remove amino acids from positions E746 to A750 (notably ΔE746_A750), but many subtypes exist with varying start and end points and sometimes insertions or substitutions[1][2][4][7]. The mutations occur within the kinase domain's β3–αC loop—a critical region for enzymatic activity—resulting in increased autophosphorylation and constitutive activation of downstream signaling pathways such as AKT and STAT. This leads to enhanced cell survival and proliferation. These mutations are among the most frequent activating alterations found in non-small cell lung cancer (NSCLC), accounting for about half of all EGFR mutations detected clinically[2][4]. Tumors harboring these deletions are highly sensitive to several generations of EGFR tyrosine kinase inhibitors (TKIs) including erlotinib, gefitinib, afatinib, osimertinib, and lapatinib. The presence of an EGFR exon 19 deletion is a well-established predictive biomarker for response to these targeted therapies. There is significant heterogeneity among different subtypes regarding their clinical behavior and sensitivity to various TKIs; however, all confer increased sensitivity compared with wild-type EGFR[5][7]. Resistance can develop over time due to secondary mutations or alternative pathway activation. In summary: EGFR exon 19 deletions define a class-defining oncogenic driver alteration that is both diagnostically actionable as a biomarker and therapeutically targetable with multiple approved drugs in NSCLC patients[1][2][3][4].

Other names

EGFR 19delEGFR ΔE746_A750EGFR delE746_A750Epidermal growth factor receptor exon 19delErbB1 exon 19 deletion

Inhibition of mutant EGFR tyrosine kinase activity by competitive binding to the ATP-binding site, blocking downstream signaling pathways that drive cell proliferation and survival[1][3][4].