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. Knockdown of NF1 led to PLX4720 resistance in-vitro. MEK inhibition with AZD6244 (selumetinib) had some efficacy but was also less active than in NF1 proficient cells. 4 patients with mutant alleles of NF1 were identified among patients relapsed after vemurafenib. Of these, one was a nonsense mutation (p.R2450*) present in both pretreatment and postrelapse biopsies. The patient had a progression-free survival (PFS) of about 10 weeks. The other NF1 mutations were silent events (patient 15, c.135T>C, patient 45 c.4023G>A, and patient 50 c3018C>T) located within candidate splicing motifs. Patients 15 and 50 exhibited response rates of relatively short duration (10 and 12 weeks, respectively) and the mutations were observed in both the pretreatment and postrelapse biopsies. Patient 45 experienced a PFS of 5 months, and the NF1 mutation was only present in the postrelapse biopsy indicative of acquired resistance.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1470
- Gene URL
- https://civic.genome.wustl.edu/links/genes/3867
- Variant URL
- https://civic.genome.wustl.edu/links/variants/587
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Skin Melanoma
- Evidence Direction
- Supports
- Drug
- Vemurafenib
- Evidence Level
- C
- Clinical Significance
- Resistance
- Pubmed
- 23288408
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Vemurafenib | Resitance or Non-Reponse | true |