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MET Testing
The method used for detecting MET aberrations in NSCLC depends on the type of aberration present*
PROTEIN OVEREXPRESSION
IHC†
IHC†
Uses antibodies against tumor antigens to measure levels of protein
VARIANT DETECTION
NGS‡
NGS10‡
High-throughput method used to determine the nucleotide sequence of entire genomes or a broad panel of target genes
VARIANT DETECTION
RT-PCR†
RT-PCR11†
Used to amplify specific targets and detect alternative variants that lead to exon skipping
VARIANT DETECTION
Sanger Sequencing†
Sanger Sequencing10†
Determines the nucleotide sequence of DNA and is used when analyzing small regions of DNA on a limited number of samples or genomic targets
CHROMOSOMAL ABNORMALITIES
FISH†
FISH12†
Utilizes fluorescent probes that bind to specific DNA sequences to identify chromosomal abnormalities
MET aberrations and their corresponding testing methods
c-Met Overexpression2–3†
METex14 Skipping Mutations4–6‡
MET Gene Amplification4,7–9†
c-Met Overexpression2–3†
METex14 Skipping Mutations4–6‡
MET Gene Amplification4,7–9†
*Not all methods shown here are FDA-approved for MET testing. There are no FDA-approved tests for c-Met overexpression or MET gene amplification13
†Non-FDA approved testing methodologies for MET aberrations.13‡NGS testing is FDA-approved as a CDx for METex14 skipping mutations.13
CDx=companion diagnostic; FDA=Food and Drug Administration; FISH=fluorescence in situ hybridization; IHC=immunohistochemistry; MET=mesenchymal-epithelial transition; NGS=next-generation sequencing; NSCLC=non-small cell lung cancer; RT-PCR=reverse transcription polymerase chain reaction.
Magaki S, Hojat SA, Wei B, So A, Yong WH. An introduction to the performance of immunohistochemistry. Methods Mol Biol. 2019;1897:289-298. doi:10.1007/978-1-4939-8935-5_25
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
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
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
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
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
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
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
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
NGS vs. Sanger Sequencing. Illumina. Accessed August 10, 2023. https://www.illumina.com/science/technology/next-generation-sequencing/ngs-vs-sanger-sequencing.html
The basics: RT-PCR. Thermo Fisher Scientific. Accessed August 10, 2023. https://www.thermofisher.com/us/en/home/references/ambion-tech-support/rtpcr-analysis/general-articles/rt--pcr-the-basics.html
Fluorescence in situ hybridization (FISH). Genome.gov. Updated August 21, 2023. Accessed August 22, 2023. https://www.genome.gov/genetics-glossary/Fluorescence-In-Situ-Hybridization
List of cleared or approved companion diagnostic devices. US Food and Drug Administration. Updated August 21, 2023. Accessed August 22, 2023. https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-orapproved-companion-diagnostic-devices-in-vitro-and-imaging-tools
