T790M
•
In 50-60% of AR cases
•
Substitution of threonine to methionine at amino-acid position 790 in
exon 20 of EGFR gene enhances the ATP affinity of the kinase domain
of the EGFR-mutant receptor restoring its affinity for ATP to that of
wt
•
Minor clones with T790M+ with low allelic frequencies identified in
treatment-naïve tumors
–
Pressure from TKIs may select for enriched growth of these T790M
clones, leading to AR
•
T790M in patients with a germline polymorphism (rarely seen),
associated with familial cancer syndromes
