Annotation Detail
Information
- Associated Genes
- DDX43
- Associated Variants
-
DDX43 OVEREXPRESSION
(
ENST00000370336.5 )
DDX43 OVEREXPRESSION ( ENST00000370336.5 ) - Associated Disease
- uveal melanoma
- Source Database
- CIViC Evidence
- Description
- MEK inhibitor-resistant (selumetinib, PD0325901, GSK1129212) uveal melanoma cell lines were created from two GNAQ Q209L mutant cell lines. Overexpression of DDX43 mediated RAS-induced selumetinib resistance as demonstrated by depletion of DDX43 decreasing RAS proteins and ectopic expression of DDX43 induced RAS protein levels. These results were confirmed using biopsies from liver metastases in 14 patients with uveal melanoma harboring GNAQ or GNA11 mutations who were treated on a phase II study of selumetinib. 6 patients with partial response or stable disease for ≥16 weeks, were defined as “responders” (R), 8 patients who had disease progression before 16 weeks were defined as “nonresponders” (NR). DDX43 Expression (qPCR) was higher in nonresponders (P = 0.045). Liver metastasis biopsy samples (3 R and 3 NR) were immunoblotted for DDX43, pERK and RAS proteins with consistent results.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1135
- Gene URL
- https://civic.genome.wustl.edu/links/genes/13005
- Variant URL
- https://civic.genome.wustl.edu/links/variants/481
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Uveal Melanoma
- Evidence Direction
- Supports
- Drug
- Selumetinib,Trametinib,MEK Inhibitor PD0325901
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 24899684
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| MEK Inhibitor PD0325901 | Resitance or Non-Reponse | true |
| Selumetinib | Resitance or Non-Reponse | true |
| Trametinib | Resitance or Non-Reponse | true |