Annotation Detail

Information
Associated Genes
ERBB2
Associated Variants
ERBB2 AMPLIFICATION ( ENST00000269571.10 )
ERBB2 AMPLIFICATION ( ENST00000269571.10 )
Associated Disease
Her2-receptor positive breast cancer
Source Database
CIViC Evidence
Description
The HER2/Neu mammary tumor mouse model MMTV-NeuT was employed to demonstrate dependence of HER2 tumor formation on PIK3 p110alpha isoform. MMTV-NeuT mice were crossed with floxed p110alpha mice. Diassacociated tumors cells from these mice were treated with Cre adenovirus to delete p110alpha, or GFP adenovirus, and cells were transplanted into athymic mice. GFP treated cells formed new tumors, while p110alpha deletion blocked tumor formation indicating tumor dependence on PI3KA. Next, MMTV-NeuT tumors were dissociated and treated with pan-PI3K inhibitor GDC-0941. Reduced lipid kinase activity and reduced phospho-Akt levels were seen in these cells. Administration of 125 mg/kg GDC-0941 to athymic mice with transplantation of tumor cells caused marked reduction of tumor cell volume in comparison to control treatment.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1380
Gene URL
https://civic.genome.wustl.edu/links/genes/20
Variant URL
https://civic.genome.wustl.edu/links/variants/306
Rating
3
Evidence Type
Predictive
Disease
Her2-receptor Positive Breast Cancer
Evidence Direction
Supports
Drug
Pictilisib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
22802530
Drugs
Drug NameSensitivitySupported
PictilisibSensitivitytrue