Annotation Detail
Information
- Associated Genes
- MET
- Associated Variants
-
MET p.Asp1246Val (p.D1246V)
(
ENST00000318493.11,
ENST00000397752.8 )
MET p.Asp1246Val (p.D1246V) ( ENST00000318493.11, ENST00000397752.8 ) - Associated Disease
- lung non-small cell carcinoma
- Source Database
- CIViC Evidence
- Description
- Case report of a patient with lung adenocarcinoma harboring both a mutation in EGFR and an amplification of MET. After progression on erlotinib the patient was treated with combined type I MET (savolitinib) and EGFR (osimertinib) inhibition and responded. When resistance developed, a new MET kinase domain mutation, D1228V, was detected. Drug binding predictions and in vitro studies demonstrated that the D1228V mutation induces resistance to type I but not type II MET TKIs. The patient was treated with erlotinib (EGFR TKI) combined with cabozantinib, a type II MET inhibitor, and had a response which continued at the time of report (5 months).
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1865
- Gene URL
- https://civic.genome.wustl.edu/links/genes/52
- Variant URL
- https://civic.genome.wustl.edu/links/variants/798
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Lung Non-small Cell Carcinoma
- Evidence Direction
- Supports
- Drug
- Savolitinib
- Evidence Level
- C
- Clinical Significance
- Resistance
- Pubmed
- 27694386
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Savolitinib | Resitance or Non-Reponse | true |