Annotation Detail

Information

Associated Genes: ROS1
Associated Variants: ROS1 CD74-ROS1 L2155S
Associated Disease: lung non-small cell carcinoma
Source Database: CIViC Evidence
Description: The L2155S mutation in ROS1 was identified in the HCC78CR1, -2 and -3 cell lines which harbor the SLC34A2–ROS1 rearrangement and in 2 patients with NSCLC with progressive disease following crizotinib treatment and CD74–ROS1 rearrangment. Crystal structure predicted ROS1 L2155S mutation to be highly destabilizating and cause protein structural modification. HCC78CR1, 2, and 3 cells and Ba/F3 cells transfected with CD74–ROS1 L2155S, showed resistance to crizotinib compared with parental HCC78 and Ba/F3 cells. In addition, these cell lines showed resistance to foretinib, a potent ROS1 inhibitor that is effective against ROS1 G2032R-mutant cells (16), and TAE684, a potent ALK inhibitor
Variant Origin: somatic
Variant Origin: Somatic
Evidence URL: https://civic.genome.wustl.edu/links/evidence_items/1256
Gene URL: https://civic.genome.wustl.edu/links/genes/4941
Variant URL: https://civic.genome.wustl.edu/links/variants/517
Rating: 3
Evidence Type: Predictive
Disease: Lung Non-small Cell Carcinoma
Evidence Direction: Supports
Drug: Foretinib,Crizotinib,TAE684
Evidence Level: D
Clinical Significance: Resistance
Pubmed: 25688157

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