Annotation Detail

Information
Associated Genes
ERBB2
Associated Variants
ERBB2 p.Tyr772_Ala775dup (p.Y772_A775dup) ( ENST00000541774.5, ENST00000269571.10, ENST00000445658.6, ENST00000406381.6, ENST00000584450.5, ENST00000584601.5 )
ERBB2 p.Tyr772_Ala775dup (p.Y772_A775dup) ( ENST00000269571.10, ENST00000406381.6, ENST00000445658.6, ENST00000541774.5, ENST00000584450.5, ENST00000584601.5 )
Associated Disease
lung carcinoma
Source Database
CIViC Evidence
Description
Human HER2 with YVMA insertion was put under a clara cell specific, rtTA promoter system inducible via doxycycline. Induction of mutant HER2 in these mice drove rapid development of adenosquamous lung tumors, where tumor maintenance was dependent on continued YMVA HER2 induction by doxycycline. Administration of afatinib had a stronger effect than erlotinib or trastuzumab, as measured by histology and tumor volume regression. Authors state that in the case of afatinib vs. trastuzumab, intracellular HER2 signaling may be blocked by afatanib but remain unaltered by trastuzumab.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1047
Gene URL
https://civic.genome.wustl.edu/links/genes/20
Variant URL
https://civic.genome.wustl.edu/links/variants/414
Rating
4
Evidence Type
Predictive
Disease
Lung Carcinoma
Evidence Direction
Supports
Drug
Afatinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
19122144
Drugs
Drug NameSensitivitySupported
AfatinibSensitivitytrue