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 non-small cell carcinoma
Source Database
CIViC Evidence
Description
The NSCLC cell line NCI-H1975 carrying the EGFR T790M mutation was resistant to erlotinib but showed increased sensitivity to HKI-272 (neratinib, IC50: 0.29 μmol/L). In an in vitro study Ba/F3 cells transfected with either EGFR-L858R or EGFR-L858R/T790M were used to assay cell growth. Ba/F3 cells require IL-3 in order to proliferate, but cells transfected with an activated oncogene are IL-3 independent. Cells with an EGFR L858R/T790M mutation demonstrated an improved response to neratinib (IC50: 0.185umol/L vs. >10umol/L) compared to the same cells treated with erlotinib.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/2162
Gene URL
https://civic.genome.wustl.edu/links/genes/19
Variant URL
https://civic.genome.wustl.edu/links/variants/34
Rating
2
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Neratinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
16818618
Drugs
Drug NameSensitivitySupported
NeratinibSensitivitytrue