MET alterations (exon 14 skipping or amplification)
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-MET |
|---|---|
| Type | Biomarker |
| Aliases | MET alterationsMET amplificationMET ex14METex14Альтерації MET (пропуск екзону 14 або амплифікація) |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025 SRC-ONCOKB |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"functional_impact": "Loss of CBL-mediated ubiquitination (ex14) or constitutive HGF-independent signaling (amplification)", "gene": "MET", "gene_hugo_id": "HGNC:7029", "hotspots": ["exon 14 skipping (MET ex14 / METex14, splice-site disruption around exon 14)", "MET amplification (high-level: GCN ≥10 or MET/CEP7 ≥4)"], "variant_type": "splice / amplification"} |
| Measurement | MethodTumor-tissue NGS (DNA + RNA panel preferred for ex14) OR ctDNA NGS OR FISH (amplification) OR IHC screening Unitscategorical (ex14: positive/negative); copy number ratio (amplification) Sensitivity requirementRNA-NGS preferred for ex14 to capture splice-site variants outside hotspots; FISH for amplification (MET/CEP7 ≥4 = high) |
| Related biomarkers | BIO-EGFR-MUTATION |
Notes
MET ex14 occurs in ~3–4% of NSCLC adenocarcinoma; enriched in older patients, sarcomatoid histology. Capmatinib (GEOMETRY mono-1) and tepotinib (VISION) are approved for ex14-positive advanced NSCLC. High-level MET amplification (GCN ≥10) drives a subset of HCC and papillary RCC and is an actionable resistance mechanism in EGFR-mutant NSCLC progressing on osimertinib (combine osimertinib + savolitinib in trials).
Used By
Actionability
BMA-MET-AMP-GASTRIC- MET amplification in gastric / GEJ adenocarcinoma (~5%): preclinical rationale strong but...BMA-MET-AMP-HCC- MET amplification / overexpression in HCC has biological rationale (HGF/MET autocrine loo...BMA-MET-AMP-NSCLC- High-level MET amplification in NSCLC: capmatinib activity in high-amp cohort of GEOMETRY...BMA-MET-AMP-RCC-PAPILLARY- MET-driven papillary type-1 RCC: cabozantinib superior to sunitinib in MET-driven pRCC (P...BMA-MET-EX14-NSCLC- MET exon 14 skipping in advanced NSCLC (~3-4% of adenocarcinoma): capmatinib (GEOMETRY mo...
Biomarker
BIO-MET-AMPLIFICATION- MET amplification (high-level copy-number gain)
Indications
IND-NSCLC-2L-MET-AMP-CAPMATINIB- IND-NSCLC-2L-MET-AMP-CAPMATINIBIND-NSCLC-2L-MET-EX14-CAPMATINIB- IND-NSCLC-2L-MET-EX14-CAPMATINIBIND-NSCLC-2L-MET-EX14-TEPOTINIB- IND-NSCLC-2L-MET-EX14-TEPOTINIBIND-NSCLC-2L-PD-L1-POST-IO-DOCETAXEL- IND-NSCLC-2L-PD-L1-POST-IO-DOCETAXELIND-RCC-NON-CLEAR-CELL-1L-CABOZANTINIB- IND-RCC-NON-CLEAR-CELL-1L-CABOZANTINIB
Questionnaires
QUEST-NSCLC-1L-STUB- Non-small cell lung cancer — first line
Red flag
RF-NSCLC-MET-EX14-ACTIONABLE- MET exon 14 skipping — ~3-4% of NSCLC adenocarcinoma; older / smoker enriched. Capmatinib...