Annotation Detail

Information
Associated Genes
EGFR
Associated Variants
EGFR p.Leu858Arg (p.L858R) ( ENST00000275493.7, ENST00000450046.2, ENST00000455089.5 )
EGFR p.Leu858Arg (p.L858R) ( ENST00000275493.7, ENST00000450046.2, ENST00000455089.5 )
Associated Disease
cancer
Source Database
CIViC Evidence
Description
MCF-7 cells were transduced with YFP tagged EGFR with E746_A750delELREA mutation, or YFP EGFR wildtype, and stained for ectopic YFP EGFR and phospho-Akt as a readout for EGFR pathway activity. Increased p-Akt stain was seen with ectopic mutant EGFR over wildtype cells. Parallel erlotinib incubations of cells with wildtype EGFR induced recompartmentalization of ectopic EGFR protien only at high concentration (10uM). Addition of erlotinib to mutant EGFR cell incubations reduced p-Akt signal and induced recompartmentalization of ectopic EGFR protien at considerably lower conecntration (100 nM) erlotinib. These results indicate the EGFR L858R variant as a growth pathway driver targetable by erlotinib.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/4265
Gene URL
https://civic.genome.wustl.edu/links/genes/19
Variant URL
https://civic.genome.wustl.edu/links/variants/33
Rating
3
Evidence Type
Predictive
Disease
Cancer
Evidence Direction
Supports
Drug
Erlotinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
17877814
Drugs
Drug NameSensitivitySupported
ErlotinibSensitivitytrue