MET

Overview

MET is a receptor tyrosine kinase and an established actionable driver in LUAD via exon 14 skipping and amplification.

Alterations observed in the corpus

  • Altered more often in LUAD metastases than in matched primaries PMID:37084736.
  • MET amplification and exon 14 skipping mutations were detected in CSF ctDNA from lung cancer patients with CNS involvement in the csf_msk_2024 cohort (1,007 CSF samples, 711 patients); resistance mutation p.Y1230N emerged on crizotinib therapy PMID:39289779.
  • Recurrent SNVs in anaplastic thyroid carcinoma (ATC) identified by SeqSig analysis PMID:38412093.
  • Co-amplification detected in ctDNA at progression in HER2+ esophagogastric cancer (EGC) treated with pembrolizumab + trastuzumab; MET IHC expression confirmed in escape lesions; identified as resistance mechanism PMID:37406106.
  • MET amplification (post-treatment enrichment) confirmed as an acquired resistance mechanism to EGFR-targeted therapy in NSCLC in the MSK-CHORD (n=24,950) real-world cohort; enrichment pattern consistent across NLP-annotated treatment lines. PMID:39506116
  • In 2,336 MSK PDAC patients (pdac_msk_2024), MET amplification was identified in the context of other-MAPK-mutant PDAC (KRAS-WT) fusions and activating alterations in the MAPK pathway; MET is not among the primary drivers highlighted in the KRAS-mutant 95% majority but its status in the KRAS-WT subtype is part of the alternative-driver landscape. PMID:39753968
  • MET amplification and fusion detected in patient ctDNA at resistance to KRASG12C + EGFR inhibition in CRC PMID:36355783
  • MET amplification in 5 GBC patients (OncoKB level 3B actionable) PMID:36228155
  • MET mutation and amplification assessed in advanced NSCLC immunotherapy cohort; neither reached significance for PFS outcomes (P = 0.81 and P = 0.42) PMID:36038778
  • MET amplification and expression were characterized across 947 cancer cell lines in the CCLE pharmacogenomic profiling study, enabling correlation with sensitivity to targeted drugs PMID:22460905
  • Copy-number amplification in Basal-like breast cancer; listed among druggable RTK targets (alongside FGFR1/2, IGF1R, KIT, PDGFRA) in TCGA 510-tumor analysis PMID:23000897
  • Alteration in ~2% of high-grade urothelial bladder tumors; part of the RTK–RAS–RAF pathway alteration landscape PMID:23897969
  • RTK intratumoral heterogeneity: co-existing EGFR/PDGFRA/MET alterations within individual GBM tumors cannot be resolved by bulk profiling; MET noted as part of the RTK alteration landscape in GBM PMID:24120142
  • High expression supported MET-inhibitor therapy recommendations in patients PN13 and PN15 in a WGTA study of rare metastatic neuroendocrine neoplasms PMID:24326773
  • Altered in rhabdomyosarcoma as a known downstream target of the PAX3-FOXO1 fusion oncogene; pathway-level alteration implicated in PAX3-FOXO1-driven oncogenesis (P=1.54×10⁻³) PMID:24436047
  • MET is mutated in ~3% of HCC and located at a 7q31 focal amplification; high MET expression is used as an enrichment biomarker for tivantinib trials in HCC PMID:24735922
  • Overexpression associated with poor prognosis and sorafenib resistance in HCC; tivantinib failed in MET-high HCC (mechanism may be MET-independent); capmatinib and cabozantinib (which inhibits MET alongside VEGFRs) still under evaluation PMID:24798001
  • Compensatory activation implicated in EGFR-inhibitor resistance via reactivation of PI3K/AKT and MAPK and promotion of EMT in NPC; co-targeted by GEN1286 (EGFR×MET bispecific ADC) PMID:24952746
  • MET recurrent exon 2 (30%) and exon 18/19 (17%) alternative splicing in gastric cancer (EGC); RTK amplification in CIN subtype; potential therapeutic relevance PMID:25079317
  • MET DNA mutations in 7% of LUAD; exon 14 skipping (alternative splicing) in 4% (10/230) with identifiable cis-acting splice-site mutations in 9/10 cases; focal amplification enriched in oncogene-negative tumours; nominated as driver and therapeutic target PMID:25079552
  • Recurrent activating kinase-domain mutations (p.Val1088Ala, p.Ile1095Thr, p.Phe1218Ile) and extracellular p.Asp153Tyr identified in 15% of pRCC; chr7 amplification of the MET locus in ~70% of pRCCs; induced as downstream target of ACTG1-MITF fusion; major therapeutic rationale for MET inhibitors in pRCC PMID:25401301
  • MET not a primary driver in PTC per this TCGA integrated analysis; the dominant drivers are BRAF, RAS, RET/NTRK fusions, and EIF1AX PMID:25417114
  • MET identified as a recurrent HBV integration site in intrahepatic CCA, suggesting viral-mediated MET oncogene activation in HBV-associated iCCA PMID:25526346
  • MET is listed as a candidate RTK alteration in HNSC (TCGA, n=279); alternative exon-14 skipping transcript detected in 2 HPV(−) tumours by structural variant analysis. PMID:25631445
  • MET amplified in 1% of HCC (243-case European WES cohort); co-alteration with HGF (3% frequency) in the MET/HGF RTK axis; listed as FDA-targetable in the druggable landscape PMID:25822088
  • Focal amplifications in 2 desmoplastic melanoma tumors, IHC-confirmed; identified as a targetable RTK alteration with potential therapeutic implications PMID:26343386
  • Identified as a marker of the reactive-like ILC mRNA subtype (characterized by high EGFR overexpression) in a comprehensive molecular analysis of invasive lobular carcinoma PMID:26451490
  • LINE-element insertion fusion involving MET detected in a single periampullary (DUOAC) tumor lacking KRAS/TP53 mutations, with high MET expression PMID:26804919
  • MET significantly mutated exclusively in lung adenocarcinoma vs other TCGA tumor types (q<0.1); MET-CAPZA2 novel fusion and KIF5B-MET previously reported fusion identified; MET and ERBB2 high-level amplifications enriched in tumors lacking other RTK/Ras/Raf activating events (p<0.01) PMID:27158780
  • Lower frequency in young lung cancer (YLC) patients; MET exon 14 skipping is age-skewed: 0.72% (≤50 yrs), 1.1% (51–69 yrs), 3.25% (>70 yrs); pivotal tepotinib and capmatinib trials enrolled patients up to 74 years old PMID:27346245
  • Alteration contributing to the actionable alteration list in recurrent/metastatic head and neck cancers, alongside MAX, MCL1, KDR, and MYCN PMID:27442865
  • Harbors H1094Y pathogenic missense mutation in a single unclassified RCC (uRCC) case (T62), suggesting overlap with papillary RCC and providing a candidate MET-directed therapeutic target PMID:27713405
  • Exon 14 alterations in prospective LUAD cohort (860 patients, MSK-IMPACT): 65.4% matched therapy rate with 76.5% clinical benefit; wild-type MET amplification 16.7% matched (50% benefit) PMID:28336552
  • Included in the targetable-alteration tally recovered by broad-panel sequencing vs amplicon panels and shallow WES in a 62-tumor-type pan-cancer cohort PMID:28481359
  • MET amplification or oncogenic mutation was identified in 5% of esophagogastric cancer (EGC) patients in the MSK cohort; MET was one of several potentially targetable kinase targets frequently co-occurring with other RTK-RAS-PI3K alterations, suggesting combination strategies may be needed for clinical actionability PMID:29122777
  • Altered in 3% of NSCLC patients in this MSK-IMPACT cohort; too few events for response analysis to anti-PD-(L)1 therapy PMID:29337640

Cancer types (linked)

  • LUAD — metastasis-enriched alteration in the MSK organotropism cohort (n=2,532) PMID:37084736.
  • NSCLC — MET amplification and exon 14 skipping detected in CSF ctDNA; resistance mutation p.Y1230N on crizotinib; capmatinib used as targeted therapy PMID:39289779.
  • Anaplastic thyroid carcinoma (ATC) — recurrent SNVs by SeqSig PMID:38412093.
  • Esophagogastric cancer (EGC) — co-amplification at progression; resistance mechanism to trastuzumab-based therapy PMID:37406106.

Co-occurrence and mutual exclusivity

  • None reported.

Therapeutic relevance

  • MET exon 14 skipping and amplification in CSF ctDNA are actionable; capmatinib was used as targeted therapy in the MSK CSF cohort. Resistance mutation p.Y1230N emerged on crizotinib, informing treatment switch PMID:39289779.
  • MET co-amplification at progression identifies acquired resistance to trastuzumab in HER2+ EGC; serial ctDNA monitoring can detect MET amplification before radiographic progression PMID:37406106.

Open questions

  • Whether metastasis-emergent MET alterations in LUAD are clinically actionable at the point of re-biopsy is not resolved; the paper reports only ~4% of metastases carried new actionable alterations overall PMID:37084736.

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:36355783

This page was processed by entity-page-writer on 2026-05-15. - PMID:36228155

This page was processed by entity-page-writer on 2026-05-15. - PMID:36038778

This page was processed by entity-page-writer on 2026-05-15. - PMID:22460905

This page was processed by entity-page-writer on 2026-05-15. - PMID:23000897

This page was processed by entity-page-writer on 2026-05-15. - PMID:23897969

This page was processed by entity-page-writer on 2026-05-15. - PMID:24120142

This page was processed by entity-page-writer on 2026-05-15. - PMID:24326773

This page was processed by entity-page-writer on 2026-05-15. - PMID:24436047

This page was processed by entity-page-writer on 2026-05-15. - PMID:24735922

This page was processed by entity-page-writer on 2026-05-15. - PMID:24798001

This page was processed by entity-page-writer on 2026-05-15. - PMID:24952746

This page was processed by entity-page-writer on 2026-05-15. - PMID:25079317

This page was processed by entity-page-writer on 2026-05-15. - PMID:25079552

This page was processed by entity-page-writer on 2026-05-15. - PMID:25401301

This page was processed by entity-page-writer on 2026-05-15. - PMID:25417114

This page was processed by entity-page-writer on 2026-05-15. - PMID:25526346

This page was processed by entity-page-writer on 2026-05-15. - PMID:25631445

This page was processed by entity-page-writer on 2026-05-15. - PMID:25822088

This page was processed by entity-page-writer on 2026-05-15. - PMID:26343386

This page was processed by entity-page-writer on 2026-05-15. - PMID:26451490

This page was processed by entity-page-writer on 2026-05-15. - PMID:26804919

This page was processed by entity-page-writer on 2026-05-15. - PMID:27158780

This page was processed by entity-page-writer on 2026-05-15. - PMID:27346245

This page was processed by entity-page-writer on 2026-05-15. - PMID:27442865

This page was processed by entity-page-writer on 2026-05-15. - PMID:27713405

This page was processed by entity-page-writer on 2026-05-15. - PMID:28336552

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