It's Time to DISCOVER MET in NSCLC

  • Did you know?
    The MET pathway is dysregulated in NSCLC1,2
    MET/c-Met protein expression, MET gene amplification, and METex14 skipping mutations contribute to disease pathogenesis and have been linked to poor prognosis
    Learn more about MET Aberrations in NSCLC
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ex14=exon 14; MET=mesenchymal-epithelial transition; NSCLC=non-small cell lung cancer.

MET Aberrations

MET signaling in NSCLC is dysregulated through mechanisms including, but not limited to, high c-Met protein overexpression, MET gene amplification, METex14 skipping mutations, and HGF overexpression. MET aberrations have been linked to poor prognosis in NSCLC3-7

Overview
High c-Met protein overexpression*
MET Gene Amplification
METex14 Skipping Mutations

Depending on the testing methodology and patient population, MET aberration prevalence can be up to:

MET Aberrations
MET Aberrations

The prevalence of biomarkers does not indicate relative efficacy or safety of associated therapies. Some biomarkers may have greater characterization across various patient populations.

*Threshold for c-Met protein overexpression is ≥50% tumor cells with strong (3+) staining intensity. †EGFR-WT NSQ NSCLC.

EGFR=epidermal growth factor receptor; ex14=exon 14; HGF=hepatocyte growth factor; MET=mesenchymal-epithelial transition; NSCLC=non-small cell lung cancer; NSQ=non-squamous; WT=wild type.

c-Met Protein Overexpression
Cause4,8
Changes in epigenetic, transcriptional, and post-transcriptional regulation
Prevalence3,17,18
~13–17%†
Role as a Biomarker7
Actionable biomarker in NSCLC
Method of Detection5,6
IHC
c-Met Protein Overexpression

*Threshold for c-Met protein overexpression is ≥50% tumor cells with strong (3+) staining intensity. †EGFR-WT NSQ NSCLC.

EGFR=epidermal growth factor receptor; ex14=exon 14; HGF=hepatocyte growth factor; IHC=immunohistochemistry; MET=mesenchymal-epithelial transition; NSCLC=non-small cell lung cancer; NSQ=non-squamous; WT=wild type.

MET Gene Amplification
Cause4
Increase in the number of copies of the MET gene
Prevalence4
~2–5%
Role as a Biomarker9*
Emerging biomarker
Method of Detection10-12
FISH, NGS, RT-PCR
MET Gene Amplification

*Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed March 31, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

ex14=exon 14; FISH=fluorescence in situ hybridization; HGF=hepatocyte growth factor; MET=mesenchymal-epithelial transition; NGS=next-generation sequencing; NSCLC=non-small cell lung cancer; RT-PCR=reverse transcription polymerase chain reaction.

METex14 Skipping Mutations
Cause4,8
Disruption in mRNA splicing, resulting in the loss of a key regulatory domain and impaired c-Met protein degradation
Prevalence4
~2–4%
Role as a Biomarker7
Actionable biomarker in NSCLC
Method of Detection10,13-16
NGS, RT-PCR, Sanger Sequencing
METex14 Skipping Mutations

ex14=exon 14; HGF=hepatocyte growth factor; MET=mesenchymal-epithelial transition; NGS=next-generation sequencing; NSCLC=non-small cell lung cancer; RT-PCR=reverse transcription polymerase chain reaction.

Learn more about the methods
used to test for MET aberrations
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References
  1. Guo B, Cen H, Tan X, Liu W, Ke Q. Prognostic value of MET gene copy number and protein expression in patients with surgically resected non-small cell lung cancer: a meta-analysis of published literatures. PLoS One. 2014;9(6):e99399. doi:10.1371/journal.pone.0099399.
  2. Lee GD, Lee SE, Oh DY, et al. MET exon 14 skipping mutations in lung adenocarcinoma: Clinicopathologic implications and prognostic values. J Thorac Oncol. 2017;12(8):1233-1246. doi:10.1016/j.jtho.2017.04.031.
  3. Motwani M, Panchabhai S, Bar J, et al. P60.12 Prevalence of c-Met overexpression (c-Met+) and impact of prior lines of treatment on c-Met protein expression in NSCLC. J Thorac Oncol. 2021;16(10):S1169-S1170. doi:10.1016/j. jtho.2021.08.633.
  4. Liang H, Wang M. MET oncogene in non-small cell lung cancer: Mechanism of MET dysregulation and agents targeting the HGF/c-Met axis. Onco Targets Ther. 2020;13:2491-2510. doi:10.2147/OTT.S231257.
  5. Park S, Choi YL, Sung CO, et al. High MET copy number and MET overexpression: Poor outcome in non-small cell lung cancer patients. Histol Histopathol. 2012;27(2):197-207. doi:10.14670/HH-27.197.
  6. Sun W, Song L, Ai T, et al. Prognostic value of MET, cyclin D1 and MET gene copy number in non-small cell lung cancer. J Biomed Res. 2013;27(3):220-230. doi:10.7555/JBR.27.20130004.
  7. List of cleared or approved companion diagnostic devices. US Food and Drug Administration. Updated March 5, 2025. Accessed March 31, 2025. https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools.
  8. Gherardi E, Birchmeier W, Birchmeier C, Vande Woude G. Targeting MET in cancer: Rationale and progress. Nat Rev Cancer. 2012;12(2):89-103. doi:10.1038/nrc3205.
  9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed March 31, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  10. Michaels E, Bestvina CM. Meeting an un-MET need: Targeting MET in non-small cell lung cancer. Front Oncol. 2022;12:1004198. doi:10.3389/fonc.2022.1004198.
  11. Das R, Jakubowski MA, Spildener J, Cheng YW. Identification of novel MET exon 14 skipping variants in non-small cell lung cancer patients: A prototype workflow involving in silico prediction and RT-PCR. Cancers (Basel). 2022;14(19):4814. doi:10.3390/cancers14194814.
  12. Kim EK, Kim KA, Lee CY, et al. Molecular diagnostic assays and clinicopathologic implications of MET exon 14 skipping mutation in non-small-cell lung cancer. Clin Lung Cancer. 2019;20(1):e123-e132. doi:10.1016/j.cllc.2018.10.004.
  13. Fang L, Chen H, Tang Z, et al. MET amplification assessed using optimized FISH reporting criteria predicts early distant metastasis in patients with non-small cell lung cancer. Oncotarget. 2018;9(16):12959-12970. doi:10.18632/oncotarget.24430.
  14. Peng LX, Jie GL, Li AN, et al. MET amplification identified by next-generation sequencing and its clinical relevance for MET inhibitors. Exp Hematol Oncol. 2021;10(1):52. doi:10.1186/s40164-021-00245-y.
  15. Cai YR, Zhang HQ, Zhang ZD, Mu J, Li ZH. Detection of MET and SOX2 amplification by quantitative real-time PCR in non-small cell lung carcinoma. Oncol Lett. 2011;2(2):257-264. doi:10.3892/ol.2010.229.
  16. NGS vs. Sanger Sequencing. Illumina. Accessed August 10, 2023. https://www.illumina.com/science/technology/next-generation-sequencing/ngs-vs-sanger-sequencing.html.
  17. Le X, Aggarwal C, Simmons A, et al. 1303P - METPRO: Evaluating prognostic value of c-Met protein overexpression and concurrent biomarker presence. Ann Oncol. 2024;35(suppl 2):S289. doi:10.1016/j.annonc.2024.08.1360.
  18. Cortot AB, Dubois R, Gregoire V, et al. 165P - Consistency analysis of c-Met protein expression over time in patients with non-squamous non-small cell lung cancer. Ann Oncol. 2024;35(suppl 2):S282. doi:10.1016/j.annonc.2024.08.0173.
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MET amplification is an emerging biomarker and in clinical research as a potential therapeutic target. Prognosis statements and prevalence estimates are based on multiple sources; survival and prevalence data can vary among studies and datasets because of detection methodology used, patient sample sizes and/or demographics/characteristics. Some patients may have more than one MET aberration and may have overlap with other NSCLC biomarkers.