What it is: What it is: The EGFR (epidermal growth factor receptor) gene encodes a receptor for tyrosine kinase on the cell surface. Binding to the receptor leads to activation of the RAS, RAF and MEK signaling pathways, leading to uncontrolled cell proliferation. The most frequent mutations involve L858R and deletions of exon 19. Mutations in exon 20 cause resistance to treatment with tyrosine kinase inhibitors. In particular, the T790M mutation in exon 20 leads to resistance to first- and second-generation tyrosine kinase inhibitors (TKIs) but responds to third generation TKIs (osimertinib).

Why the test is done:: In NSCLC, the presence of EGFR mutations predict sensitivity to tyrosine kinase inhibitors.
Frequency: Approximately in 10-15% of the Western world
1. Mostly in non-smoking women
2. Most common in East Asia
3. More common in adenocarcinomas, and particularly in well-differentiated