Annotation Detail

Information
Associated Genes
ERBB2
Associated Variants
ERBB2 p.Thr862Ala (p.T862A) ( ENST00000584450.5, ENST00000584601.5, ENST00000541774.5, ENST00000445658.6, ENST00000269571.10, ENST00000406381.6 )
ERBB2 p.Thr862Ala (p.T862A) ( ENST00000269571.10, ENST00000406381.6, ENST00000445658.6, ENST00000541774.5, ENST00000584450.5, ENST00000584601.5 )
Associated Disease
stomach carcinoma
Source Database
CIViC Evidence
Description
Cell proliferation analysis showed that the ERBB2-H878Y mutant had the highest sensitivity against lapatinib among all mutations tested. Another mutation, ERBB2-V777L also remained sensitive to lapatinib with a cellular IC50 value similar to that of wild type ERBB2. Remaining mutations showed a shift towards significant higher cellular IC50 values compared to the wild type receptor. Since levels of up to 1 µM of lapatinib may be achieved in patients, ERBB2-V773A, ERBB2-T862A and ERBB2-N857S mutations might respond to higher doses of lapatinib. In contrast, ERBB2-L755S, ERBB2-L755P and ERBB2-T798M caused strong lapatinib resistance.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1986
Gene URL
https://civic.genome.wustl.edu/links/genes/20
Variant URL
https://civic.genome.wustl.edu/links/variants/871
Rating
3
Evidence Type
Predictive
Disease
Stomach Carcinoma
Evidence Direction
Supports
Drug
Lapatinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
22046346
Drugs
Drug NameSensitivitySupported
LapatinibSensitivitytrue