https://orcid.org/0000-0003-0083-9896
Figures & data
Table 1. Active studies with MET-targeted therapies in advanced or metastatic METex14 NSCLC: summary of ongoing trials [Citation17–22,Citation44,Citation77]
Figure 1. Biology of MET exon 14 skipping mutation (METex14). (A) Left, Exon 14 of the MET gene encodes the juxtamembrane domain of the MET receptor. Right, METex14 eliminates this key regulatory region, which could lead to increased stability and increased kinase activity of the MET receptor and, ultimately, upregulated signaling of the MET pathway [Citation34]. (B) Alterations leading to METex14 result in a messenger RNA in which exons 13 and 15 are fused [Citation10,Citation34,Citation36,Citation45]. Arrows indicate the primary regions of interest for sequencing to detect METex14. HGF, hepatocyte growth factor; MET, mesenchymal–epithelial transition; mRNA, messenger RNA; P, phosphorylation; Ub, ubiquitin. Cortot AB et al, Exon 14 Deleted MET Receptor as a New Biomarker and Target in Cancers, Journal of the National Cancer Institute, 2017, 109, 5, djw262, adapted by permission of Oxford University Press
![Figure 1. Biology of MET exon 14 skipping mutation (METex14). (A) Left, Exon 14 of the MET gene encodes the juxtamembrane domain of the MET receptor. Right, METex14 eliminates this key regulatory region, which could lead to increased stability and increased kinase activity of the MET receptor and, ultimately, upregulated signaling of the MET pathway [Citation34]. (B) Alterations leading to METex14 result in a messenger RNA in which exons 13 and 15 are fused [Citation10,Citation34,Citation36,Citation45]. Arrows indicate the primary regions of interest for sequencing to detect METex14. HGF, hepatocyte growth factor; MET, mesenchymal–epithelial transition; mRNA, messenger RNA; P, phosphorylation; Ub, ubiquitin. Cortot AB et al, Exon 14 Deleted MET Receptor as a New Biomarker and Target in Cancers, Journal of the National Cancer Institute, 2017, 109, 5, djw262, adapted by permission of Oxford University Press](/cms/asset/66af63e5-5d8c-42eb-82db-4e3370cbf46c/iery_a_1924683_f0001_oc.jpg)
Table 2. Association of METex14 with poor overall survival [Citation4,Citation5,Citation13,Citation14,Citation43]
Figure 2. Overview of the amplicon-based and hybrid capture–based NGS methods. (a) Amplicon-based NGS methods utilize PCR primers that are designed to amplify targeted regions of interest in the genome [Citation45,Citation47]. Alterations (indels or base substitutions) that affect primer binding within the target region or are located outside of the target region (such as within intronic regions flanking MET exon 14) may go undetected. (b) Hybrid capture–based NGS methods use oligonucleotide probes to isolate larger regions of interest in the tumor genome, including regions flanking the targeted area [Citation47]. Allele dropout is less likely to occur, as long probes used for hybridization can tolerate mutations within the genomic DNA. Furthermore, DNA sequences outside of the target region (such as intronic regions flanking MET exon 14) can be captured and sequenced. NGS, next-generation sequencing; PCR, polymerase chain reaction. Adapted with permission from Elsevier: Journal of Molecular Diagnostics, 19/3, Jennings LJ et al, Guidelines for Validation of Next-Generation Sequencing–Based Oncology Panels: A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists, 341–365, copyright 2017
![Figure 2. Overview of the amplicon-based and hybrid capture–based NGS methods. (a) Amplicon-based NGS methods utilize PCR primers that are designed to amplify targeted regions of interest in the genome [Citation45,Citation47]. Alterations (indels or base substitutions) that affect primer binding within the target region or are located outside of the target region (such as within intronic regions flanking MET exon 14) may go undetected. (b) Hybrid capture–based NGS methods use oligonucleotide probes to isolate larger regions of interest in the tumor genome, including regions flanking the targeted area [Citation47]. Allele dropout is less likely to occur, as long probes used for hybridization can tolerate mutations within the genomic DNA. Furthermore, DNA sequences outside of the target region (such as intronic regions flanking MET exon 14) can be captured and sequenced. NGS, next-generation sequencing; PCR, polymerase chain reaction. Adapted with permission from Elsevier: Journal of Molecular Diagnostics, 19/3, Jennings LJ et al, Guidelines for Validation of Next-Generation Sequencing–Based Oncology Panels: A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists, 341–365, copyright 2017](/cms/asset/d509b8f9-7698-4f51-a986-6720c59a034c/iery_a_1924683_f0002_oc.jpg)