Annotation Detail
Information
- Associated Genes
- BRAF
- Associated Variants
-
BRAF APC
BRAF APC - Associated Disease
- melanoma
- Source Database
- CIViC Evidence
- Description
- In a retrospective study of 44 relapsed melanoma patients harboring BRAF V600E or V600K (known BRAF inhibitor sensitizing mutations), MAPK pathway reactivation mechanisms were implicated in acquired resistance to BRAF inhibitor (vemurafenib or dabrafenib) monotherapy. The following MAPK pathway variants were found in progressive tumors with patient matched baseline tumors (some patients donated samples from multiple geographically/temporally distinct progressive tumors): NRAS mutations (G12D, G12R, G13R, Q61K, Q61R, Q61L) in 13/71 (18%) of progressive tumors, KRAS mutations (G12C, G12R, Q61H) in 5/71 (7%) of progressive tumors, mutant BRAF amplification (2-15 fold or 4-75 copies) in 11/57 (19%) of progressive tumors, mutant BRAF alternative splice variants (novel exon boundaries between 1/9, 1/11, 3/9) in 6/48 (13%) of progressive tumor RNA.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/6400
- Gene URL
- https://civic.genome.wustl.edu/links/genes/5
- Variant URL
- https://civic.genome.wustl.edu/links/variants/2226
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Melanoma
- Evidence Direction
- Supports
- Drug
- Dabrafenib,Vemurafenib
- Evidence Level
- B
- Clinical Significance
- Resistance
- Pubmed
- 24265155
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Dabrafenib | Resitance or Non-Reponse | true |
| Vemurafenib | Resitance or Non-Reponse | true |