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Review
. 2021 Apr 13:5:PO.20.00516.
doi: 10.1200/PO.20.00516. eCollection 2021.

MET Exon 14 Skipping Mutations in Non-Small-Cell Lung Cancer: An Overview of Biology, Clinical Outcomes, and Testing Considerations

Mark A Socinski  1 , Nathan A Pennell  2 , Kurtis D Davies  3
Affiliations
Review

MET Exon 14 Skipping Mutations in Non-Small-Cell Lung Cancer: An Overview of Biology, Clinical Outcomes, and Testing Considerations

Mark A Socinski et al. JCO Precis Oncol. .
No abstract available

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Mark A. SocinskiSpeakers' Bureau: AstraZeneca, Bristol-Myers Squibb, Celgene, Genentech, Merck, Novartis Research Funding: AstraZeneca, Bristol-Myers Squibb, Genentech, Merck, Novartis, TakedaNathan A. PennellConsulting or Advisory Role: Amgen, AstraZeneca, Bristol-Myers Squibb, Cota, Eli Lilly, Genentech, Inivata, Merck, Pfizer Open Payments Link: https://openpaymentsdata.cms.gov/physician/204570/summaryKurtis D. DaviesConsulting or Advisory Role: Novartis Travel, Accommodations, Expenses: Archer No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Driver mutations involved in NSCLC. Adenocarcinoma, the most common NSCLC histology, can be further characterized by various oncogenic drivers. Many of these oncogenic drivers have an FDA-approved targeted therapy available.,,, FDA, US Food and Drug Administration; NSCLC, non–small-cell lung cancer.
FIG 2.
FIG 2.
MET exon 14 skipping alterations by site and regions of interest for sequencing. (A) To detect these potential alterations, it is important to sequence both exon 14 and its surrounding regions. The regions where known alterations leading to exon 14 skipping can occur are mapped onto the schematic of the MET gene. MET exon 14 skipping alterations in any of these regions will result in an mRNA where exons 13 and 15 are fused.,,, (B) An analysis of 1,387 samples found that a plurality of MET exon 14 skipping events occur at the donor site; however, events are spread across and around exon 14.
FIG 3.
FIG 3.
Treatment responses in clinical trials with MET inhibitors. (A) Best overall response in patients with advanced METex14 NSCLC who were treated with crizotinib in the PROFILE 1001 trial. Patients in this trial were a mix of treatment naive and previously treated. (B) Best overall response per BIRC in patients with advanced METex14 NSCLC who were treated with tepotinib in the VISION trial. Patients in this trial were a mix of treatment naive and previously treated; data are shown from the analysis by line of treatment.,, (C) Best overall response per BIRC in patients with advanced METex14 NSCLC who were treated with capmatinib in the GEOMETRY mono-1 trial. Patients in cohort 5b were treatment naive and received capmatinib in the first-line setting. Patients in cohorts 6 and 4 were previously treated and received capmatinib in the second-line setting and the second- or third-line setting, respectively. (D) Best overall response in patients with advanced METex14 NSCLC who were treated with savolitinib in trial NCT02897479. Patients in this trial were a mix of treatment naive and previously treated; data are shown from the analysis by line of treatment. 1/2/3L, first-/second-/third-line; BIRC, blinded independent review committee; METex14, MET exon 14 skipping mutation; NSCLC, non–small-cell lung cancer.
FIG 4.
FIG 4.
Overview of the (A) amplicon-based and (B) hybrid capture–based DNA NGS methods for targeted sequencing of MET. Amplicon-based NGS methods use polymerase chain reaction primers to amplify the regions of interest. Some alterations that lead to MET exon 14 skipping may prevent these primers from binding, leading to false negatives. Hybrid capture–based NGS methods use longer probes to pull down regions of interest, preventing the problem of allele dropout observed in the amplicon-based method and reducing false negatives.,,,, NGS, next-generation sequencing.
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