Annotation Detail

Information
Associated Genes
NF1
Associated Variants
NF1 MUTATION
NF1 MUTATION
Associated Disease
skin melanoma
Source Database
CIViC Evidence
Description
NF1 was identified in an unbiased RNAi screen as mediator of resistance to BRAF inhibition in BRAF mutant melanoma. BRAF V600E/NF1 mutant cell lines were sensitive to ERK inhibition with VTX-11e, modest resistance was observed against RAF inhibitor AZ628. Combined PLX4720 and AZD6244 (selumetinib) achieved greater efficacy than either agent alone but NF1 knockdown was still associated with residual resistance to combined RAF/MEK inhibition in vitro.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1471
Gene URL
https://civic.genome.wustl.edu/links/genes/3867
Variant URL
https://civic.genome.wustl.edu/links/variants/587
Rating
2
Evidence Type
Predictive
Disease
Skin Melanoma
Evidence Direction
Supports
Drug
VTX-11e,AZ628
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
23288408
Drugs
Drug NameSensitivitySupported
AZ628Sensitivitytrue
VTX-11eSensitivitytrue