EGFR T790M

Variant type

missense mutation

Location

Chromosome 7

Exon

21

Protein change

p.T790M

cDNA change

-

Genomic coordinate

Chromosome 7

FATHMM prediction

-

Variant category

I

Variant description

The T790M mutation results in an amino acid substitution at position 790 of EGFR, from a threonine (T) to a methionine (M). This mutation occurs within exon 20, which encodes part of the kinase domain. The frequency of EGFR T790M mutation in EGFR-mutated NSCLC is <5% of untreated EGFR mutant tumors (PMID: 16912157). The T790M mutation occurs at a critical “gatekeeper” residue in the ATP-binding pocket of EGFR, analogous to the T315I mutation in imatinibresistant BCR-ABL (PMID: 11423618). This change in EGFR was thought to impair binding of erlotinib or gefitinib (PMID: 12196540), but recent data suggests that it may alter the binding affinity of drug versus ATP (PMID: 18227510). The T790M mutation by itself has also been shown to increase kinase activity and oncogenic potential. The T790M mutation can be detected as a "second-site mutation" in more than 50% of EGFR-mutant lung cancers that have developed acquired resistance to erlotinib or gefitinib (PMID: 17671201).

Variant frequence

This section displays the distribution of mutated samples and tissue types (top 5).

Accoiciated drug