Annotation Detail
Information
- Associated Genes
- ALK
- Associated Variants
- ALK p.Phe1245Cys (p.F1245C) ALK p.Phe1245Cys (p.F1245C)
- Associated Disease
- lung non-small cell carcinoma
- Source Database
- CIViC Evidence
- Description
- A 52 year old with a non-smoking history was diagnosed with stage IV NSCLC-adenocarcinoma and treated with chemotherapy. Upon disease progression, the initial diagnostic biopsy tested positive for ALK-rearrangement using break apart FISH, but the ALK fusion was not sequenced for mutations. Break-apart signal was positive in 66% of tumor cells. Crizotinib was initiated and a sustained near complete response for 27 months was observed, after which an FDG-avid cervical lymph node appeared along with pleural effusions and pleural nodules. A pleural nodule was biopsied and profiled using hybrid-capture next generation sequencing, and revealed EML4-ALK variant 3 with F1245C mutation at mutant allele frequency of 2% and tumor purity of 13%. Crizotinib was maintained for 8 additional months due to low tumor burden and slow progression.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1339
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1
- Variant URL
- https://civic.genome.wustl.edu/links/variants/551
- Rating
- 2
- Evidence Type
- Predictive
- Disease
- Lung Non-small Cell Carcinoma
- Evidence Direction
- Supports
- Drug
- Crizotinib
- Evidence Level
- C
- Clinical Significance
- Resistance
- Pubmed
- 26775591
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Crizotinib | Resitance or Non-Reponse | true |