EGFR Mutation Study (10 Common Mutations)

Common EGFR mutations include exon 19 deletions and the exon 21 L858R point mutation (both sensitizing to EGFR inhibitors). Other frequent alterations are exon 20 insertions and the T790M resistance mutation (exon 20). Less common activating variants include G719X (exon 18), S768I (exon 20), and L861Q (exon 21). These mutations guide targeted therapy choices.

The most common EGFR resistance mutation is T790M — a threonine-to-methionine substitution at amino acid 790. It arises in roughly 50–60% of patients with acquired resistance to first- and second‑generation EGFR tyrosine kinase inhibitors, increases ATP affinity at the kinase “gatekeeper” residue, and reduces drug binding. Detection guides use of third‑generation inhibitors effective against T790M.

The EGFR mutation test detects changes in the EGFR gene in cancer cells, usually from a tumor biopsy or a blood (liquid biopsy) sample. It identifies mutations (for example exon 19 deletions, L858R, T790M) that predict response or resistance to EGFR-targeted therapies, helping oncologists choose appropriate tyrosine kinase inhibitors and guide prognosis and treatment planning.

EGFR exon 20 insertion mutations are in-frame insertions within exon 20 of the epidermal growth factor receptor gene that alter the kinase domain’s shape, producing constitutive receptor activation. They occur in a subset of non-small cell lung cancers and are generally less sensitive to first- and second-generation EGFR tyrosine kinase inhibitors, often requiring newer targeted agents developed specifically for this mutation class.

Classical EGFR mutations are the common activating alterations in non–small cell lung cancer, chiefly exon 19 deletions and the exon 21 L858R point mutation. These alterations increase EGFR kinase activity and typically confer sensitivity to EGFR tyrosine kinase inhibitors. They are most frequent in adenocarcinomas, especially among non‑smokers, females, and East Asian patients; other uncommon variants can affect treatment response.

HER2 mutation refers to changes in the ERBB2 gene that lead to overproduction or abnormal activity of the HER2 receptor, a cell-surface tyrosine kinase. This drives rapid cell growth and is implicated especially in certain breast and gastric cancers. HER2 alterations affect prognosis and guide use of targeted therapies (for example, trastuzumab, pertuzumab, tyrosine kinase inhibitors) to block HER2-driven signaling.