Annotation Detail
Information
- Associated Genes
- EGFR
- Associated Variants
-
EGFR p.Thr790Met (p.T790M)
(
ENST00000275493.7,
ENST00000450046.2,
ENST00000455089.5 )
EGFR p.Thr790Met (p.T790M) ( ENST00000275493.7, ENST00000450046.2, ENST00000455089.5 ) - Associated Disease
- lung cancer
- Source Database
- CIViC Evidence
- Description
- Lung cancers can accumulate activating mutations in oncogenes such as EGFR. The common L858R EGFR mutation has been shown previously to be sensitive to small molecular tyrosine kinase inhibitors (ie. erlotinib). In response, tumors may accumulate an additional 'gatekeeper' mutation in EGFR, T790M. Authors show that T790M retain low affinity for gefitinib and that introduction of T790M in the presence of L858R mutant increases the ATP affinity of L858R and activates wild-type EGFR, thus showing that increased ATP affinity is the primary mode of resistance in tumors with T790M, though irreversible ATP inhibitors (ie. HKI-272) are able to overcome this resistance via covalent bonding.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/642
- Gene URL
- https://civic.genome.wustl.edu/links/genes/19
- Variant URL
- https://civic.genome.wustl.edu/links/variants/34
- Rating
- 5
- Evidence Type
- Predictive
- Disease
- Lung Cancer
- Evidence Direction
- Supports
- Drug
- Multikinase Inhibitor AEE788,Gefitinib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 18227510
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Gefitinib | Resitance or Non-Reponse | true |
| Multikinase Inhibitor AEE788 | Resitance or Non-Reponse | true |