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MET amplification (high-level copy-number gain)

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

IDBIO-MET-AMPLIFICATION
TypeBiomarker
Aliases
MET CN-ampMET HLAMET amplificationMET high-level amplificationMET ампліфікація (високорівневе підвищення копій гена)
Statusreviewed 2026-04-29 | pending_clinical_signoff
DiseasesNone declared
SourcesSRC-ESMO-NSCLC-METASTATIC-2024 SRC-GEOMETRY-WOLF-2020 SRC-NCCN-NSCLC-2025

Biomarker Facts

Biomarker typecopy_number
Mutation details{"functional_impact": "Constitutive HGF-independent MET signaling (high-level CN-amp)", "gene": "MET", "gene_hugo_id": "HGNC:7029", "variant_type": "amplification"}
Measurement
MethodFISH (MET/CEP7 ratio) preferred; tumor-tissue NGS or ctDNA NGS with copy-number calling acceptable; IHC alone is screening only
UnitsMET/CEP7 ratio (≥4.0 = high-level) OR mean MET gene-copy-number (GCN) per cell (≥10 = high-level)
Sensitivity requirementConcordance between FISH and NGS imperfect; thresholds vary by assay (Cappuzzo/Schildhaus criteria most-cited). Low-level amp (GCN 5-9) NOT actionable as monotherapy target.
Related biomarkersBIO-MET BIO-EGFR-MUTATION

Notes

Distinct from MET ex14 skipping (BIO-MET parent entity covers both; this entity is the high-level CN-amp subset). Two clinical contexts: (1) De-novo MET-amp NSCLC (~1-5% high-level) — capmatinib (GEOMETRY mono-1 high-amp cohort: ORR 40%, mPFS 5.5 mo; off-label expansion beyond ex14 label) and tepotinib (VISION cohort B). (2) Acquired MET-amp post-osimertinib resistance in EGFR-mut NSCLC — osimertinib + savolitinib (SAVANNAH; ORR ~49%; not yet FDA-approved). High-level MET amplification also drives subsets of HCC and papillary RCC. Critical: low-level amp (GCN 5-9) NOT actionable — must be high-level (GCN ≥10 OR MET/CEP7 ≥4.0).

Used By

Indications