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
- colorectal cancer
- Source Database
- CIViC Evidence
- Description
- 5 of 7 colorectal cancer (CRC) cell lines with BRAF V600E mutation were resistant to treatment with the BRAF inhibitor vemurafenib. An RNAi screen in the WiDr cell line (a V600E CRC line) identified EGFR as an enhancer for survival when exposed to vemurafenib. Treatment with vemurafenib and EGFR inhibitor (cetuximab or gefitinib) in V600E CRC cells (WiDr, VACO432 and KM20) showed inhibited growth as well as induction of the cleaved PARP apoptotic marker. WiDr and VACO432 cells were injected into immunodeficient mice. Modest response was seen with vemurafenib treatment, while combination treatment showed considerable tumor growth inhibition as compared to control.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1408
- Gene URL
- https://civic.genome.wustl.edu/links/genes/5
- Variant URL
- https://civic.genome.wustl.edu/links/variants/12
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Colorectal Cancer
- Evidence Direction
- Supports
- Drug
- Cetuximab,Vemurafenib,Gefitinib
- Evidence Level
- D
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 22281684
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Cetuximab | Sensitivity | true |
| Gefitinib | Sensitivity | true |
| Vemurafenib | Sensitivity | true |