Description
Mesenchymal Epithelial Transition MET is a prototypical receptor tyrosine kinase. Its ligand is Hepatocyte Growth Factor (HGF). MET alterations are drivers of human cancer. Amplification and resulting overexpression has been reported in several cancers, and make the receptor's activity independent of HGF. Gene fusions also decouple kinase activity from the cell membrane and render it constitutively active. Finally, exclusion of the juxtamembrane (JM) domain of the kinase by "skipping" of exon 14 activates the kinase. FDA-approved selective MET inhibitors, including tepotinib and capmatinib, have shown efficacy in cancers with exon 14 skipping mutations or MET amplification.
Cyan = gene · Slate = variant · Green = drug · Click variant to filter table
Variants (8)
| CIViC ID | Name | HGVS | Type(s) |
|---|---|---|---|
| 270 | Amplification | transcript_amplification | |
| 649 | D1228N D1246N,ASP1246ASN,ASP1228ASN | NC_000007.13:g.116423407G>A,NC_000007.14:g.116783353G>A,ENST00000397752.8:c.3682G>A,ENSP00000380860.3:p.Asp1228Asn,ENST00000397752.7:c.3682G>A,ENSP00000380860.3:p.Asp1228Asn,NM_000245.4:c.3682G>A,NP_000236.2:p.Asp1228Asn,NM_000245.3:c.3682G>A,NP_000236.2:p.Asp1228Asn | missense_variant |
| 798 | D1228V ASP1228VAL,D1246V,ASP1246VAL | ENST00000318493.11:c.3737A>T,ENSP00000317272.6:p.Asp1246Val,NM_001127500.3:c.3737A>T,NP_001120972.1:p.Asp1246Val | missense_variant |
| 324 | Exon 14 Skipping Mutation | exon_loss_variant | |
| 323 | Mutation | transcription_variant,gain_of_function_variant | |
| 621 | Overexpression | ||
| 2774 | R1004G ARG1004GLY | NC_000007.14:g.116771971C>G,NC_000007.13:g.116412025C>G,ENST00000397752.8:c.3010C>G,ENSP00000380860.3:p.Arg1004Gly,NM_000245.4:c.3010C>G,NP_000236.2:p.Arg1004Gly | missense_variant |
| 4386 | Splice Site (c.3028G>A) EXON 14 SPLICE DONOR VARIANT | NC_000007.14:g.116771989G>A,NC_000007.13:g.116412043G>A,ENST00000397752.8:c.3028G>A,NM_000245.4:c.3028G>A | splice_donor_variant |