Annotation Detail
Information
- Associated Genes
- ALK
- Associated Variants
- ALK EML4-ALK T1151INST
- Associated Disease
- lung non-small cell carcinoma
- Source Database
- CIViC Evidence
- Description
- A lung adenocarcinoma patient responded to crizotinib treatment for 12 months, after which the cancer relapsed and sequencing of the ALK tyrosine kinase domain revealed a 1151insT mutation. This mutation was not found in the pre-crizotinib biopsy. EML4-ALK T1151insT was expressed In Ba/F3 cells and an IC50 of 431.8 nM was obtained, which was 16 times higher than for EML4-ALK wild-type, indicating strong crizotinib resistance. EML4-ALK containing H3122 NSCLC cells were incubated in increasing levels of crizotinib inducing resistance. The resulting cell line H3122 CR2 had IC50 10x greater to crizotinib than parental H3122, and was found to contain 1151 insT mutation. In western blots, pALK levels in H3122 CR2 cells remained apparent under 1000 nM crizotinib, whereas pALK signal was ablated under these conditions in parental H3122 cells.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/444
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1
- Variant URL
- https://civic.genome.wustl.edu/links/variants/173
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Lung Non-small Cell Carcinoma
- Evidence Direction
- Supports
- Drug
- Crizotinib
- Evidence Level
- C
- Clinical Significance
- Resistance
- Pubmed
- 22277784
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Crizotinib | Resitance or Non-Reponse | true |