Annotation Detail
Information
- Associated Genes
- ROS1
- Associated Variants
-
ROS1 p.Gly2032Arg (p.G2032R)
(
ENST00000368507.8,
ENST00000368508.7 )
ROS1 p.Gly2032Arg (p.G2032R) ( ENST00000368507.8, ENST00000368508.7 ) - Associated Disease
- lung adenocarcinoma
- Source Database
- CIViC Evidence
- Description
- Resistance to crizotinib developed in a patient with metastatic lung adenocarcinoma harboring a CD74-ROS1 rearrangement who had initially shown a dramatic response to treatment. A biopsy of a resistant tumor showed an acquired G2032R mutation in the ROS1 kinase domain. Although this mutation does not lie at the gatekeeper residue, it confers resistance to ROS1 kinase inhibition through steric interference with drug binding. The same resistance mutation was observed at all the metastatic sites that were examined at autopsy, suggesting that this mutation was an early event in the clonal evolution of resistance.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/2934
- Gene URL
- https://civic.genome.wustl.edu/links/genes/4941
- Variant URL
- https://civic.genome.wustl.edu/links/variants/1271
- Rating
- 1
- Evidence Type
- Predictive
- Disease
- Lung Adenocarcinoma
- Evidence Direction
- Supports
- Drug
- Crizotinib
- Evidence Level
- C
- Clinical Significance
- Resistance
- Pubmed
- 23724914
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Crizotinib | Resitance or Non-Reponse | true |