Annotation Detail
Information
- Associated Genes
- ALK
- Associated Variants
- ALK p.Ile1171Thr (p.I1171T) ALK p.Ile1171Thr (p.I1171T)
- Associated Disease
- lung non-small cell carcinoma
- Source Database
- CIViC Evidence
- Description
- The I1171T mutation in ALK fusions was found in a NSCLC patient shown positive for ALK rearrangement via break apart FISH assay, who progressed after 8 months of crizotinib, and then progressed again after 4 months of alectinib. The MGH056-1 cell line was derived from this patient, and this cell line was resistant to alectinib. Sequencing of MGH056-1 cells revealed the I1171T mutation in ALK. In cell culture studies Ba/F3 cells with EML4-ALK I1171T required more that 10x the concentration of alectinib to significantly reduce viability that was required for EML4-ALK wild-type expressing cells. Computer simulation studies indicated that the I1171T mutation interfered with alectinib binding at the ALK active site.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1283
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1
- Variant URL
- https://civic.genome.wustl.edu/links/variants/527
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Lung Non-small Cell Carcinoma
- Evidence Direction
- Supports
- Drug
- Alectinib
- Evidence Level
- C
- Clinical Significance
- Resistance
- Pubmed
- 25228534
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Alectinib | Resitance or Non-Reponse | true |