Annotation Detail

Information
Associated Genes
MET
Associated Variants
MET AMPLIFICATION ( ENST00000318493.11 )
MET AMPLIFICATION ( ENST00000318493.11 )
Associated Disease
colorectal cancer
Source Database
CIViC Evidence
Description
Case report of a patient with BRAF V600E mutant metastatic colorectal cancer. Combined EGFR and BRAF inhibition (panitumumab and vemurafenib) showed an initial partial response for 4 months. Re-biopsy at the time of progression showed a MET amplification and overexpression (IHC, ISH) but no secondary mutations in candidate resistance genes (EGFR, KRAS, NRAS, MAP2K1). MET amplification was also present in a subset of tumor cells in the pretreatment sample. MET amplification was also identified in 3/17 (18%) chemonaive BRAF V600E colorectal cancer tumor tissues. Overexpression of MET in a BRAF mutant CRC cell line (WiDr) confered resistance to combined vemurafenib and panitumumab. The addition of crizotinib to this combination restored sensitivity in vitro. The patient was started on combined vemurafenib and crizotinib in January 2016 and had a metabolic, clinical and tumor marker response that was ongoing at the time of publication (06/16) without significant toxicity.
Variant Origin
N/A
Variant Origin
N/A
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1588
Gene URL
https://civic.genome.wustl.edu/links/genes/52
Variant URL
https://civic.genome.wustl.edu/links/variants/270
Rating
4
Evidence Type
Predictive
Disease
Colorectal Cancer
Evidence Direction
Supports
Drug
Crizotinib,Vemurafenib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
27325282
Drugs
Drug NameSensitivitySupported
CrizotinibSensitivitytrue
VemurafenibSensitivitytrue