Annotation Detail

Information
Associated Genes
BRAF
Associated Variants
BRAF p.Val640Glu (p.V640E) ( ENST00000288602.11, ENST00000496384.7, ENST00000644969.2, ENST00000646891.2 )
BRAF p.Val640Glu (p.V640E) ( ENST00000288602.11, ENST00000496384.7, ENST00000644969.2, ENST00000646891.2 )
Associated Disease
melanoma
Source Database
CIViC Evidence
Description
49 BRAF-mutant melanoma cell lines from patients not previously treated with BRAF inhibition were analyzed. 21 exhibited primary resistance to BRAF inhibition using PLX4720. Inhibition of MEK1/2 (AZD6244 [selumetinib]) and PI3K/mTOR (BEZ235 [dactolisib]) was the most effective approach to counteract resistance in comparison to inhibition with the PLX4720 (progenitor of vemurafenib)-BEZ235 (where response was assessed by apoptosis, viability, p-ERK, p-Akt inhibition).
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1005
Gene URL
https://civic.genome.wustl.edu/links/genes/5
Variant URL
https://civic.genome.wustl.edu/links/variants/12
Rating
2
Evidence Type
Predictive
Disease
Melanoma
Evidence Direction
Supports
Drug
Selumetinib,Dactolisib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
26678033
Drugs
Drug NameSensitivitySupported
DactolisibSensitivitytrue
SelumetinibSensitivitytrue