# MET amplification (gene copy number)

Source: https://onco.cc/biomarkers/met-amplification-readout/  
OnCo record `met-amplification-readout` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

MET amplification means extra copies of the MET gene, either as a primary driver in a few lung cancers or as the escape route after EGFR inhibitors. No label yet selects on it; trials define it by FISH ratio or copy number.

## Summary

MET amplification is scored by FISH as MET/CEP7 ratio (high-level at 5 or more in the Camidge classification, or 2 or more with mean copies of 10 or more) or by sequencing as gene copy number (GCN 10 or more is the common trial threshold). It occurs de novo in 1 to 4 percent of NSCLC and arises in 5 to 20 percent of EGFR-mutant cancers progressing on osimertinib, the setting of the MARIPOSA-2 and the SAVANNAH trial of osimertinib plus savolitinib (NCT03778229). No approval names MET amplification as the selection criterion; amivantamab is approved on EGFR status rather than MET, and capmatinib's label covers exon 14 skipping only.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: MET amplification; MET amp; MET copy number gain; MET/CEP7 ratio; high-level MET amplification; MET GCN >= 10
- Tags: biomarker; met; no-approval

## Notes

- Lung cancer: 2 to 3% at diagnosis (cBioPortal) and commoner as acquired resistance, in 4 of 18 specimens resistant to a first-generation EGFR inhibitor (Engelman 2007) and 4 of 75 in the larger rebiopsy series (Yu 2013). There is no agreed copy-number threshold, which is the practical problem: low-level gain accompanies the aneuploidy of a third of lung tumours, and the ratio to chromosome 7 rather than the absolute copy number is what separates focal amplification from polysomy. When it is the resistance mechanism, the EGFR inhibitor should be continued and a MET inhibitor added rather than substituted.

## Sources

- SAVANNAH (NCT03778229): https://clinicaltrials.gov/study/NCT03778229

## Connected records

- biomarkers: [c-Met protein overexpression (IHC 3+ in >= 50% of tumour cells)](https://onco.cc/biomarkers/met-overexpression/), [EGFR T790M](https://onco.cc/biomarkers/egfr-t790m/), [MET exon 14 skipping mutation](https://onco.cc/biomarkers/met-ex14/)
- cancers: [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- drugs: [Amivantamab](https://onco.cc/drugs/amivantamab/), [Capmatinib](https://onco.cc/drugs/capmatinib/), [Telisotuzumab vedotin](https://onco.cc/drugs/telisotuzumab-vedotin/), [Tepotinib](https://onco.cc/drugs/tepotinib/)
- terms: [FISH / ISH (in situ hybridisation)](https://onco.cc/terms/fish/), [Gene amplification and copy-number change](https://onco.cc/terms/gene-amplification/), [MET amplification (bypass resistance)](https://onco.cc/terms/met-amplification/)
- key papers: [Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers](https://onco.cc/key-papers/paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013/), [Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors](https://onco.cc/key-papers/paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011/), [MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling](https://onco.cc/key-papers/paper-engelman-met-amplification-gefitinib-resistance-science-2007/), [MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression](https://onco.cc/key-papers/paper-awad-met-exon-14-mutations-lung-jco-2016/)
- targets: [MET](https://onco.cc/targets/met/)

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