The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Activation of MET via Diverse Exon 14 Splicing Alterations Occurs in Multiple Tumor Types and Confers Clinical Sensitivity to MET Inhibitors
Published version of a preprint
Abstract
Focal amplification and activating point mutation of the MET gene are well-characterized oncogenic drivers that confer susceptibility to targeted MET inhibitors. Recurrent somatic splice site alterations at MET exon 14 (METex14) that result in exon skipping and MET activation have been characterized, but their full diversity and prevalence across tumor types are unknown. Here, we report analysis of tumor genomic profiles from 38,028 patients to identify 221 cases with METex14 mutations (0.6%), including 126 distinct sequence variants. METex14 mutations are detected most frequently in lung adenocarcinoma (3%), but also frequently in other lung neoplasms (2.3%), brain glioma (0.4%), and tumors of unknown primary origin (0.4%). Further in vitro studies demonstrate sensitivity to MET inhibitors in cells harboring METex14 alterations. We also report three new patient cases with METex14 alterations in lung or histiocytic sarcoma tumors that showed durable response to two different MET-targeted therapies. The diversity of METex14 mutations indicates that diagnostic testing via comprehensive genomic profiling is necessary for detection in a clinical setting. Significance: Here we report the identification of diverse exon 14 splice site alterations in MET that result in constitutive activity of this receptor and oncogenic transformation in vitro. Patients whose tumors harbored these alterations derived meaningful clinical benefit from MET inhibitors. Collectively, these data support the role of METex14 alterations as drivers of tumorigenesis, and identify a unique subset of patients likely to derive benefit from MET inhibitors. Cancer Discov; 5(8); 850–9. ©2015 AACR. See related commentary by Ma, p. 802. See related article by Paik et al., p. 842. This article is highlighted in the In This Issue feature, p. 783
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In the citing paper
“Importantly, large-scale profiling studies utilizing either whole exome sequencing or broad targeted sequencing panels in NSCLC tumors have revealed multiple non-random patterns of co-occurring or mutually exclusive mutations, which typically vary depending on the particular oncogenic driver mutation15, 34, 58–62.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“Landmark large scale sequencing studies have established a census of major KRAS co-mutations in both early-stage and advanced LUAD15, 34, 59, 62.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“Although EGFR –mutant tumors represent the prototypical oncogene-addicted LUAD subgroup that spearheaded adoption of the single-driver model, the overwhelming majority of EGFR-mutant lung tumors harbor one or more co-mutations, even when the analysis is limited to pre-defined sets of cancer-relevant genes within established panels (FoundationOne, Guardant360, MSK-IMPACT)15, 59, 72, 73.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“NKX2–1 amplification is significantly enriched in EGFR-mutant LUAD”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“earlier studies that identified a central role for WNT signaling in LUAD metastasis”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“like CTNNB1 mutations, are encountered preferentially in advanced-stage tumors15, 34, 72, 73”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“but are less likely to harbor TP53 alterations (23.8%−26.5%) compared with other driver subgroups15, 128.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“experimental data demonstrating increased invasive potential of EGFR and CTNNB1 co-mutated NSCLC cells in vitro15, 34, 72, 73, 120, 121”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“PIK3CA mutations, including classical kinase (H1074R and H1074L) and helical (E545K and E542K) domain mutations are observed in 9%−12.4% of advanced stage EGFR-mutant LUAD”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“Activating mutations in CTNNB1 represent one of the most consistently co-selected alterations in EGFR-mutant LUAD across different studies.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“advanced-stage ALK-rearrangement -positive LUAD are enriched in somatic alterations in CDKN2A (32.5%)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“and CDKN2B (26.5%)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“their prevalence increases in late-stage tumors (5.3% - 9.6%)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“these tumors are characterized by highly significant enrichment of MDM2 and CDK4 amplification (41.6%) compared with other driver oncogenes”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“both RET and ROS1 fusion-positive LUAD are characterized by high rates of concurrent CDKN2A loss (29.8% and 30.4% for RET and ROS1-rearranged tumors respectively)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“CDKN2B loss (25% and 17.7% respectively)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“The spectrum of co-occurring alterations in BRAF-mutant NSCLC mirrors the background frequency of alterations in TP53 (53.3%), LKB1 (16.2%), ATM (5.8%), NF1 (6.9%), PIK3CA (6.6%), KEAP1 (6.6%), MYC (10.8%), NKX2–1 (7.3%)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“as well as frequent mutations in RB1 (8.9%)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“whereas loss of CDKN2A (24.1%) and CDKN2B (17.5%) occur with similar frequencies to that in the overall population of patients with NSCLC15.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“both RET and ROS1 fusion-positive LUAD are characterized by high rates of concurrent CDKN2A loss (29.8% and 30.4% for RET and ROS1-rearranged tumors respectively)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“although the frequency of TP53 mutations appears to be somewhat higher compared to ALK-rearranged tumors (34.6%−45.5% for RET-and 45.6% for ROS1- rearranged tumors)15, 131.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“patients with ERBB2-mutant NSCLC exhibit preferential amplification of NKX2–1 (19.4%) and ERBB2 itself (14.4%)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“as well as amplification of MET itself15.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“CDKN2B loss (25% and 17.7% respectively)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“relative paucity of TP53 mutations”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“but the frequencies of co-mutations in TP53 (51.7%), CDKN2A (27.2%), CDKN2B (17.2%), PIK3CA (5%), CTNNB1 (4.4%) and MDM2 amplification (7.2%) are similar to that observed in the overall population of patients with NSCLC15.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“In contrast, mutations in TP53 (33.57%) are under-represented”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
In the citing paper
“although alterations in RB1, MDM2, CDKN2A (16.6%) and CDKN2B (11.2%) are less frequent within this molecular subgroup15.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
Citations
Cites
Comprehensive molecular profiling of lung adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13385 · Cited by 5,732
Somatic mutations affect key pathways in lung adenocarcinoma
Ding, L., Getz, G., Wheeler, D. A., Mardis, E. R., McLellan, M. D., Cibulskis, K., Sougnez, C., Greulich, H., Muzny, D. M., Morgan, M. B., et al. (2008) · Nature · doi:10.1038/nature07423 · Cited by 2,681
Frampton, G. M., Fichtenholtz, A., Otto, G. A., Wang, K., Downing, S. R., He, J., Schnall-Levin, M., White, J., Sanford, E. M., An, P., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2696 · Cited by 2,157
Self-citationMapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing
Imielinski, M., Berger, A. H., Hammerman, P. S., Hernandez, B., Pugh, T. J., Hodis, E., Cho, J., Suh, J., Capelletti, M., Sivachenko, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.08.029 · Cited by 1,789
Self-citationCui, J. J., Tran‐Dubé, M., Shen, H., Nambu, M. D., Kung, P., Pairish, M., Jia, L., Meng, J. J., Funk, L. A., Botrous, I., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm2007613 · Cited by 967
Use of Statins and the Risk of Death in Patients With Prostate Cancer
Yu, O. H. Y., Eberg, M., Benayoun, S., Aprikian, A. G., Batist, G., Suissa, S., & Azoulay, L. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.49.4757 · Cited by 661
The transcriptional landscape and mutational profile of lung adenocarcinomaPreprint
Seo, J., Ju, Y. S., Lee, W., Shin, J.-Y., Lee, J. J.-K., Bleazard, T., Lee, J., Jung, Y. J., Kim, J. O., Shin, J.-Y., et al. (2012) · Genome Research · doi:10.1101/gr.145144.112 · Cited by 603
Ma, P. C., Jagadeeswaran, R., Jagadeesh, S., Tretiakova, M., Nallasura, V., Fox, E. A., Hansen, M., SCHAEFER, E. M., Naoki, K., Lader, A. S., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-2650 · Cited by 576
Self-citationSpigel, D. R., Ervin, T. J., Ramlau, R., Daniel, D. B., Goldschmidt, J. H., Blumenschein, G. R., Krzakowski, M. J., Robinet, G., Godbert, B., Barlési, F., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.47.4189 · Cited by 491
Somatic Mutations Lead to an Oncogenic Deletion of Met in Lung Cancer
Kong-Beltran, M., Seshagiri, S., Zha, J., Zhu, W., Bhawe, K. M., Mendoza, N., Holcomb, T., Pujara, K., Stinson, J., Fu, L., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2749 · Cited by 491
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Exceptional Response to Crizotinib in an MET-Amplified Triple-Negative Breast Tumor
Parsons, B. M., Meier, D. R., Gurda, G. T., Lofgren, K. A., & Kenny, P. A. (2017) · JCO Precision Oncology · doi:10.1200/po.17.00070 · Cited by 8
Baldacci, S., Kherrouche, Z., Descarpentries, C., Wislez, M., Dansin, É., Furlan, A., Tulasne, D., & Cortot, A. B. (2018) · Revue des Maladies Respiratoires · doi:10.1016/j.rmr.2018.01.011 · Cited by 8
Qiu, Y., Jiang, H., Ching, W., & Ng, M. K. (2018) · Artificial Intelligence in Medicine · doi:10.1016/j.artmed.2018.09.005 · Cited by 8
Prevention of Brain Metastases: A New Frontier
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“MET mutations are present in 2–4% of patients diagnosed with NSCLC [12,16], but there is lack of information on the risk of developing BM.”
BackgroundGuérin, C., Vinchent, A., Fernandes, M., Damour, I., Laratte, A., Tellier, R., Estevam, G. O., Meneboo, J., Villenet, C., Descarpentries, C., et al. (2025) · Molecular Oncology · doi:10.1002/1878-0261.13806 · Cited by 7
“In NSCLC, about 3% of patients display a wide variety of mutations and deletions, all leading to skipping of MET exon 14 (METex14Del) [16,32 – 34], encoding the negative regulatory juxtamembrane domain of the receptor.”
Rivalland, G., Mitchell, P., Murone, C., Asadi, K., Morey, A. L., Starmans, M. H. W., Boutros, P. C., Walkiewicz, M., Solomon, B., Wright, G. M., et al. (2019) · Translational Lung Cancer Research · doi:10.21037/tlcr.2019.03.11 · Cited by 7
Genome-wide profiling of prognosis-related alternative splicing signatures in sarcoma
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“In recent years, many studies of AS have mainly focused on distinguishing “SARC-specific” AS events by molecular experiments (20-23).”
BackgroundMolecular Targets Beyond the Big 3
Reckamp, K. L. (2020) · Thoracic surgery clinics/Thorac. surg. clin. · doi:10.1016/j.thorsurg.2020.01.004 · Cited by 7
Implications of Antigen Selection on T Cell-Based Immunotherapy
Camp, F. A., & Slansky, J. E. (2021) · Pharmaceuticals · doi:10.3390/ph14100993 · Cited by 7
“ing tumorigenesis and cancer cell su vival [39,40].”
BackgroundCanadian Consensus Recommendations on the Management of MET-Altered NSCLC
Cheema, P. K., Banerji, S. O., Blais, N., Chu, Q. S.-C., Desmeules, P., Juergens, R. A., Leighl, N. B., Sheffield, B. S., Wheatley‐Price, P. F., & Melosky, B. L. (2021) · Current Oncology · doi:10.3390/curroncol28060386 · Cited by 7
Byun, J., Park, S., Ng, B. P., Liu, Y., Kim, C.-R., & Park, C. (2022) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2022.2095203 · Cited by 7
“Other mutations in mesenchymalepithelial transition factor (MET), ROS proto-oncogene 1 (ROS1), mitogen activated protein kinase pathway (MEK), or rearranged during transfection (RET) can also be observed but are less frequent in patients with NSCLC [4,9,10].”
Sun, R., Wang, Z., Zhao, J., Ren, P., Ma, J., & Guo, Y. (2023) · JCO Precision Oncology · doi:10.1200/po.22.00482 · Cited by 7
Fraser, M., Seetharamu, N., Diamond, M., & Lee, C. (2023) · Cancer Management and Research · doi:10.2147/cmar.s386799 · Cited by 7
“16 Continued expression of receptors that would have otherwise been degraded results in overactive c-MET signaling, including ligand-independent activation, and therefore in the case of tumor cells, continued cell growth.”
BackgroundSelf-citationLiang, Q., Hu, J., Yuan, Q., Yu, M., Wang, H., & Zhao, B. (2023) · British Journal of Cancer · doi:10.1038/s41416-023-02495-5 · Cited by 7
“In parallel, MET Δ 14EX is a recurrent event, occurring in approximately 3% of lung adenocarcinomas, 2% of other lung neoplasms, 0.5% of brain gliomas, and 0.5% of carcinomas of unknown primary origin [12, 13].”
InfluentialInvestigational therapies for squamous cell lung cancer: from animal studies to phase II trials
Shum, E., Wang, F., Kim, S., Perez-Soler, R., & Cheng, H. (2017) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2017.1302425 · Cited by 7
Chu, L. P., Franck, D., Parachoniak, C. A., Gregg, J. P., Moore, M. G., Farwell, D. G., Rao, S. S. D., Heilmann, A. M. F., Erlich, R., Ross, J. S., et al. (2019) · The Oncologist · doi:10.1634/theoncologist.2019-0230 · Cited by 7
Self-citationWu, S., Li, G., Zhao, X., Xiang, J., Lizaso, A., Ye, J., Shi, C., & Chen, L. (2020) · Annals of Translational Medicine · doi:10.21037/atm-20-2741 · Cited by 7
“Gain-of-function of MET signaling has been demonstrated in oncogenic processes across multiple tumor types, including lung cancer through protein overexpression, gene amplification, mutations, or abnormal gene splicing (7-11).”
BackgroundCrizotinib in ROS1 and MET Deregulated NSCLC—Letter
Wiesweg, M., Schüler, M., & Schildhaus, H. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-3740 · Cited by 7
Yuan, P., Xue, X., Qiu, T., & Ying, J. (2024) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359231221910 · Cited by 6
“6 A few anti-MET - TKIs have been developed for MET -directed targeted therapies, such as tepotinib and capmatinib, which have been approved in the United States and Japan, respectively, and savolitinib, which was approved by the National Medical Products Administration of China in June 2021, 7–9…”
BackgroundMethodVerkerk, K., van der Wel, T. J. W. T., Zeverijn, L. J., Geurts, B. S., Spiekman, I. A. C., de Wit, G. F., Roepman, P., Jansen, A. M. L., van der Noort, V., Smit, E. F., et al. (2024) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-24-1925 · Cited by 6
Molecular mechanism of type ib MET inhibitors and their potential for CNS tumors
Liu, Z., Liu, W., Shen, X., Jiang, T., Li, X., Liu, H., & Zheng, Z. (2025) · Scientific Reports · doi:10.1038/s41598-025-85631-w · Cited by 6
MET exon 14 skipping mutations in non-small-cell lung cancer a 3 years screening experience
Dhiab, R. B., Loyaux, R., Garinet, S., Bastide, M., Léonard-Goyet, S., Fabre, E., Mansuet‐Lupo, A., Gibault, L., Jouveshomme, S., Leprieur, E. G., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-99541-4 · Cited by 6
“Met exon 14 mutations are observed in 3-4% of NSCLC cases 4,5 .”
Met Activation and Carcinogenesis
Shinomiya, N., Xie, Q. R., & Woude, G. F. V. (2017) · Current human cell research and applications · doi:10.1007/978-981-10-7296-3_7 · Cited by 6
Jiang, W., Yang, N., & Zhang, Y. (2018) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2018.02.030 · Cited by 6
Popper, H., Gruber-Moesenbacher, U., Hutarew, G., Hochmair, M. J., Absenger, G., Brčić, L., Müllauer, L., Dekan, G., Setinek, U., Krenbek, D., et al. (2016) · memo - Magazine of European Medical Oncology · doi:10.1007/s12254-016-0297-x · Cited by 6
“Exon 14 splice-site mutations occur in 3% of adenocarcinomas, and in 22% of sarcomatoid carcinomas, and therefore MET should be included in carcinoma mutation panels because of the therapeutic consequences [56, 57].”
Bironzo, P., Pepe, F., Russo, G., Pisapia, P., Gragnano, G., Aquino, G., Bessi, S., Buglioni, S., Bartoccini, F., Ferrero, G., et al. (2023) · Diagnostics · doi:10.3390/diagnostics13040629 · Cited by 6
“Particularly, this multicenter observational study tried to highlight the robustness of technical workflows adopted by each participating center in the detection of the aberrant MET transcript for targeted therapy of selected NSCLC patients [7,9].”
BackgroundMethodFurqan, M., Karanth, S. S., Goyal, R., Cai, B., Rombi, J., Davis, K. L., Caro, N., & Saliba, T. R. (2024) · Future Oncology · doi:10.2217/fon-2023-1064 · Cited by 6
“Mesenchymal–epithelial transition (MET) exon 14 skipping mutation (METex14) is present in 3–4% of NSCLC [3–5] .”
BackgroundHow to Keep Up With Molecular Testing and Targeted Therapies in Lung Cancer
Malhotra, J. D., & Kim, E. S. (2024) · JCO Oncology Practice · doi:10.1200/op.24.00230 · Cited by 6
Daoud, A., & Chu, Q. S.-C. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00222 · Cited by 6
“METex14 corresponds to the juxtamembrane domain, which is involved in its degradation by ubiquitin ligase, Cbl, leading to increase in MET activity (74, 77).”
BackgroundIsaksson, S., Hazem, B., Jönsson, M., Reuterswärd, C., Karlsson, A., Griph, H., Engleson, J., Oskarsdottir, G. N., Öhman, R., Holm, K., et al. (2020) · JTO Clinical and Research Reports · doi:10.1016/j.jtocrr.2020.100013 · Cited by 6
Ma, Y., Du, Y., Wang, R., Ji, X., Wu, J., Liu, Y., Guo, X., & Zhang, Y. (2020) · Pathology - Research and Practice · doi:10.1016/j.prp.2020.153036 · Cited by 6
Jang, H., Kim, B., Kim, D., Kim, J., & Kim, H. (2020) · Indian Journal of Cancer · doi:10.4103/ijc.ijc_797_18 · Cited by 6
Fallet, V., Matton, L., Schernberg, A., Canellas, A., Cornélis, F., & Cadranel, J. L. (2021) · Translational Lung Cancer Research · doi:10.21037/tlcr-20-1152 · Cited by 6
“Actually, the most common therapeutic alterations are the epidermal growth factor receptor (EGFR) mutation (10–30%), anaplastic lymphoma kinase (ALK) rearrangements (4–6%), c-ROS oncogene 1 (ROS1) rearrangements (2–3%), B-Raf protooncogene serine/threonine kinase (BRAF) mutations (2–4%), rearranged during transfection…”
Wagener‐Ryczek, S., & Pappesch, R. (2021) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2021.1920399 · Cited by 6
Estevam, G. O., Linossi, E. M., Macdonald, C. B., Espinoza, C. A., Michaud, J. M., Coyote‐Maestas, W., Collisson, E. A., Jura, N., & Fraser, J. S. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.03.551866 · Cited by 6
Self-citationEstevam, G. O., Linossi, E., Rao, J., Macdonald, C. B., Ravikumar, A., Chrispens, K. M., Capra, J. A., Coyote-Maestas, W., Pimentel, H., Collisson, E. A., et al. (2025) · eLife · doi:10.7554/elife.101882.3 · Cited by 6
Self-citationThe role and research progress of the MET signalling pathway in targeted therapy for osteosarcoma
Su, Q., Hou, J., Du, X., Zhang, F., Zhang, P., Wang, B., & Yao, W. (2025) · Oncology Reviews · doi:10.3389/or.2025.1615111 · Cited by 5
Warashina, S., Sato, H., Zouda, M., Takahashi, M., Wada, Y., Passioura, T., Suga, H., Watanabe, Y., Matsumoto, K., & Mukai, H. (2023) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.2c01020 · Cited by 5
Du, Y., Sun, H., Shi, Z., Sui, X., Liu, B., Zheng, Z., Liu, Y., Xuan, Z., Zhong, M., Fu, M., et al. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01333-8 · Cited by 5
“…papillary renal cell carcinoma (PRCC), gastric cancer (GC), breast cancer (BC), hepatocellular carcinoma, melanoma, and glioblastoma multiforme (GBM), all of which have a high frequency of MET -related mutations (especially the exon 14 skipping alterations ( MET ex14) and amplification) [90–93].”
BackgroundChung, C., & Umoru, G. (2024) · Journal of Oncology Pharmacy Practice · doi:10.1177/10781552241242684 · Cited by 5
Cai, X., Lin, J., Li, C., Xu, T., Chen, C., Lan, B., Wang, X., Bai, S., Huang, Y.-F., Zhang, H., et al. (2024) · BMC Cancer · doi:10.1186/s12885-024-13163-z · Cited by 5
“MET alterations, including base substitutions, insertions or deletions at splice sites or in intronic noncoding regions immediately adjacent to splice acceptor sites, and perhaps whole exon deletions, can result in exon 14 skip-ping [15, 16].”
Takeda, M., Ota, M., Iwama, E., Sugawara, S., Shukuya, T., Umemura, S., Tanaka, H., Oki, M., Takahama, T., Masuda, T., et al. (2024) · Clinical Lung Cancer · doi:10.1016/j.cllc.2024.12.004 · Cited by 5
From knowledge to action: The journey toward targeting the MET pathway via MET exon 14 skipping
Bogdanska, W., & Paik, P. K. (2025) · Cancer · doi:10.1002/cncr.35782 · Cited by 5
Mutations at the splice sites of exon 14 of MET gene: a new target for sarcomatoid carcinomas?
Wislez, M., Domblides, C., Cortot, A. B., & Lemoine, A. (2016) · Annals of Translational Medicine · doi:10.21037/atm.2016.01.12 · Cited by 5
“Similar cases were also reported by Frampton (7).”
BackgroundResultSkipping the line: bringing MET exon 14 skipping mutations to the forefront of targeted therapy
Shum, E., & Halmos, B. (2016) · Translational Cancer Research · doi:10.21037/tcr.2016.03.12 · Cited by 5
A newly developed capture-based sequencing panel for genomic assay of lung cancer
Im, S.-W., Chae, J., Jang, S. S., Choi, J., Yun, J., Cha, S., Kwon, N., Jeon, Y. K., Hwang, Y., Kim, M., et al. (2020) · Genes & Genomics · doi:10.1007/s13258-020-00949-1 · Cited by 5
(2020) · PubMed Central · doi:10.3779/j.issn.1009-3419.2020.101.45 · Cited by 5
Real-World Treatment Outcomes of MET Exon14 Skipping in Non-small Cell Lung Cancer: GFPC 03-18 Study
Babey, H., Jamme, P., Curcio, H., Assié, J., Veillon, R., Doubre, H., Pérol, M., Guisier, F., Huchot, E., Decroisette, C., et al. (2023) · Targeted Oncology · doi:10.1007/s11523-023-00976-4 · Cited by 5
“METexon14 comprises a large group of genetic alterations (point mutations, insertions, deletions, complex mutations) that determine different variants [6, 7].”
BackgroundPath Less Traveled: Targeting Rare Driver Oncogenes in Non–Small-Cell Lung Cancer
Lim, S. M., Lee, J. B., Oya, Y., Nützinger, J., & Soo, R. A. (2023) · JCO Oncology Practice · doi:10.1200/op.23.00273 · Cited by 6
Li, M., Huang, J., Xing, R., Du, X., Wei, C., & Wang, H. (2025) · BMC Pulmonary Medicine · doi:10.1186/s12890-024-03437-4 · Cited by 5
Borczuk, A., Paucar, D., & Halmos, B. (2016) · Annals of Translational Medicine · doi:10.21037/atm.2016.01.15 · Cited by 5
Brigatinib in the first-line treatment of ALK+ metastatic NSCLC: safety and efficacy
Bronte, G., Cafaro, A., Pasini, L., Priano, I., Andrikou, K., Cravero, P., Burgio, M. A., Delmonte, A., & Crinò, L. (2021) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2021.1923485 · Cited by 5
“The prevalence of ALK genomic rearrangements varies between less than 1% for early-stage disease to over 4% in metastatic lung adenocarcinomas, as based on data from the PanCancer Atlas cohort of The Cancer Genome Atlas (TCGA) (n = 566) [6–8], the MSK-IMPACT study (n = 860) [9], and FoundationOne repositories (n = 526…”
BackgroundExternal Validation ofALKandROS1Fusions Detected Using an Oncomine Comprehensive Assay
Kim, S., Do, S., & Na, K. (2021) · Anticancer Research · doi:10.21873/anticanres.15274 · Cited by 5
Kolaei, F. A. Z. V., Cai, B., Kanakamedala, H., Kim, J., Doban, V., Zhang, S., & Shi, M. M. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.786124 · Cited by 5
Wilgucki, M., Yeung, V., Ho, G., Bravo, G. L., Jones, G., Reuss, J. E., Liu, S. V., & Kim, C. (2022) · JTO Clinical and Research Reports · doi:10.1016/j.jtocrr.2022.100396 · Cited by 5
“MET amplification was found to occur in up to 10% of patients with EGFR-mutant NSCLC who progress on firstgeneration EGFR TKIs.6 MET-activating point mutations, such as Y1003N, are not as widely reported.”
BackgroundPrognostic alternative splicing signature in cervical squamous cell carcinoma
Wu, H., Li, Q., Liang, L., Qiu, L., Wei, H., Huang, B., Gang‐, C., He, R., Huang, Z., Hou, W., et al. (2020) · IET Systems Biology · doi:10.1049/iet-syb.2019.0095 · Cited by 5
Клинический случай легочной формы мукормикоза у ребенка с острым лимфобластным лейкозом
Kharagezov, D. A., Lazutin, Y. N., Арменовна, М. Э., Milakin, A. G., Stateshny, O. N., Leyman, I. A., Васильевна, Ч. А., & Дмитриевич, И. К. (2021) · South Russian Journal of Cancer · doi:10.37748/2686-9039-2021-2-4-5 · Cited by 11
Rolfo, C. D., Malapelle, U., & Russo, A. (2023) · JCO Precision Oncology · doi:10.1200/po.22.00674 · Cited by 5
Epigenetic Regulation and Therapeutic Targeting of Alternative Splicing Dysregulation in Cancer
Yan, L., & Lai, M. (2025) · Pharmaceuticals · doi:10.3390/ph18050713 · Cited by 6
“In preclinical models, mutations in the splice acceptor and donor sites of MET exon 14 lead to exon skipping, offering a new therapeutic strategy for 4% of patients with lung adenocarcinoma [50,51].”
Park, J., Chelakkot, C., Nam, J., Lee, H. S., Kim, C. R., Lee, Y., Lee, M.-S., Choi, Y., & Shin, Y. K. (2025) · Targeted Oncology · doi:10.1007/s11523-025-01166-0 · Cited by 4
“In 2015, cancer genome profiling of 38,028 tumor specimens revealed two cases of MET Y1003N mutation, both from NSCLC patients [11].”
InfluentialMechanistic insights into MET exon 14 skipping mutations and their role in tumor progression
Ghosh, P., Pecora, I., & Park, M. (2025) · Biochemical Society Transactions · doi:10.1042/bst20253091 · Cited by 4
İsmayılov, R., Altundağ, Ö., & Akçalı, Z. (2025) · Immunotherapy · doi:10.1080/1750743x.2025.2580272 · Cited by 4
Wang, Y., Liu, H., Yu, N., & Xiang, X. (2023) · Current Oncology · doi:10.3390/curroncol30090616 · Cited by 4
“The application of ARMS is primarily limited by false positive results caused by non-specific primers that may be produced by WT DNA, as well as the missed detection of low-frequency mutations [19,20].”
BackgroundMolecular profiling METex14+ non-small cell lung cancer (NSCLC): Impact of histology
Marks, J. A., Gandhi, N. S., Halmos, B., Marmarelis, M. E., Kim, S. Y., Bazhenova, L. A., Ramalingam, S. S., Xiu, J., Walker, P., Oberley, M. J., et al. (2024) · Lung Cancer · doi:10.1016/j.lungcan.2024.107935 · Cited by 4
Overcoming MET-targeted drug resistance in MET-amplified lung cancer by aurora kinase B inhibition
Choi, Y., Hwang, M., Kim, J., Park, S. Y., Kim, S., Song, J. J., & Lee, Y. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2025.120001 · Cited by 4
Prakash, S., Tyagi, P., Singh, P., Rajkumar, R., & Singh, A. P. (2024) · Current Cancer Drug Targets · doi:10.2174/0115680096331827240911165227 · Cited by 8
Chen, Y., Chen, Y., Sun, Q., Hou, X., Fu, S., Jin, H., Tao, X., Yang, Y., Wang, J., Cao, Y., et al. (2024) · Histopathology · doi:10.1111/his.15383 · Cited by 4
“21,22 MET amplification has been reported in several cancers: in 3 – 10% of non-small-cell lung cancer cases, 23 8% of gastric cancers 24 and 1 – 4% of colorectal cancers.”
Oksen, D., Boutmy, E., Wang, Y., Stroh, C., Johne, A., Nisbett, A. R., & Ryder, A. B. (2025) · Clinical Lung Cancer · doi:10.1016/j.cllc.2025.01.013 · Cited by 4
Jurkiewicz, M., Yeh, R., Shu, C. A., Hsiao, S. J., MANSUKHANI, M. M., Saqi, A., & Fernandes, H. (2025) · Journal of Molecular Pathology · doi:10.3390/jmp6010005 · Cited by 4
“…of c-MET signaling has been shown to occur through somatic alterations leading to loss of exon 14, gene copy-number amplification, and occasionally as MET gene fusions [7], resulting in increased cell proliferation, survival, invasion, and met astasis, contributing to tumorigenesis and growth [1].”
Yang, Y., Mandiyan, S., Robinson, B. S., & McMahon, G. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-0026 · Cited by 4
Park, C., Oh, I., Choi, Y.-D., Jang, T. W., Lee, J. E., Ryu, J., Lee, S.-Y., & Kim, Y. (2018) · Oncology · doi:10.1159/000486896 · Cited by 4
RetractedAnderson, C. M., Laeremans, A., Wang, X.-M. M., Wu, X., Zhang, B., Doolittle, E., Kim, J., Li, N., Pimentel, H. X. Y., Park, E., et al. (2018) · Journal of Visualized Experiments · doi:10.3791/58097 · Cited by 4
Crizotinib for c-MET –amplified advanced NSCLC: a single-center experience
Tacar, S. Y., Yılmaz, M., Öz, B., & Tural, D. G. (2021) · Tumori Journal · doi:10.1177/03008916211009303 · Cited by 4
Nathany, S., & Batra, U. (2022) · Cancer Research Statistics and Treatment · doi:10.4103/crst.crst_158_22 · Cited by 4
Oncogene alterations in non-small cell lung cancer—have we MET a new target?
Dempke, W. C. M., Reuther, S., Hamid, Z., & Thoennissen, N. H. (2022) · Translational Lung Cancer Research · doi:10.21037/tlcr-22-648 · Cited by 4
“This leads to c-MET ubiquitination abrogation, increased c-MET protein stability, and impaired c-MET degradation which then, in turn, induces ligand-independent c-MET activation (11,12).”
BackgroundMET-FISH Evaluation Algorithm: Proposal of a Simplified Method
Castiglione, R., Alidousty, C., & Holz, B. (2022) · Journal of Cancer Science and Clinical Therapeutics · doi:10.26502/jcsct.5079180 · Cited by 4
Molecular Diagnosis and Targeting for Lung Cancer
Yoneda, K., & Tanaka, F. (2017) · Current human cell research and applications · doi:10.1007/978-981-10-6469-2_1 · Cited by 4
Kanemura, H., Takeda, M., & Nakagawa, K. (2020) · Translational Lung Cancer Research · doi:10.21037/tlcr-20-707 · Cited by 4
“Lung adenocarcinomas harboring METex14 alterations manifest a substantial clinical response to MET inhibition (2,20).”
BackgroundSequencing of MET Inhibitors in Lung Cancer: Have We Met the Target?
Kim, C. G., Cho, B. C., & Lim, S. M. (2021) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2021.02.017 · Cited by 4
Wallen, Z. D., Nesline, M., Tierno, M. B., Roos, A., Schnettler, E. K., Husain, H., Sathyan, P., Caveney, B. J., Eisenberg, M. T., Severson, E. A., et al. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1473327 · Cited by 4
Hu, Y., & Ou, S. I. (2025) · Lung Cancer Targets and Therapy · doi:10.2147/lctt.s547090 · Cited by 3
Self-citationsiRNA-based therapeutic candidate targeting PRDM2 for inhibition of lung cancer progression
Kumar, S., Malik, M. Z., Chaturvedi, M., Mishra, M., Donato, M. D., Casamassimi, A., Abbondanza, C., Gazzerro, P., Nguyen, C., Nuñez, N. N., et al. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118807 · Cited by 3
Adamopoulos, P. G., Athanasopoulou, K., Boti, M. A., Dimitroulis, G., Daneva, G. N., Tsiakanikas, P., & Scorilas, A. (2023) · RNA Biology · doi:10.1080/15476286.2023.2220210 · Cited by 4
“For instance, in multiple types of tumours, alternative transcripts of MET proto-oncogene (MET) contribute to the activation of MET and provide sensitivity to MET inhibitors [14].”
BackgroundMolecular Targeting in Non-Small Cell Lung Cancer: Advances in EGFR, ROS1, ALK, and MET Pathways
Rosas, D., Jones, C. X., Hunis, B., Akinbobuyi, O., Theik, N. W. Y., Alvarez-Pinzon, A. M., & Raez, L. E. (2024) · Journal of Oncology Research and Therapy · doi:10.29011/2574-710x.10214 · Cited by 3
Taniguchi, Y., Tamiya, A., Osuga, M., Harada, D., Isa, S., Nakamura, K., Mizumori, Y., Shinohara, T., Yanai, H., Nakatomi, K., et al. (2024) · BMC Pulmonary Medicine · doi:10.1186/s12890-024-03212-5 · Cited by 3
“…tumors than in early-stage tumors, indicating their functional roles in malignant progression and metastasis; contrastingly, TP53, RB1, and NKX2–1 alterations appear to occur with comparable frequencies in early-and advanced-stage tumors [20, 26–29], which is consistent with our findings.”
ResultTan, A. C., Loh, T. J., Kwang, X. L., Tan, G. S., Lim, K. H., & Tan, D. S. W. (2021) · Lung Cancer Targets and Therapy · doi:10.2147/lctt.s263610 · Cited by 4
Fujino, T., Suda, K., Sakai, K., Murakami, I., Shimizu, S., Ohara, S., Koga, T., Hamada, A., Soh, J., Nishio, K., et al. (2021) · Clinical Lung Cancer · doi:10.1016/j.cllc.2021.09.005 · Cited by 3
Hanrahan, A. J., Iyer, G., & Solit, D. B. (2020) · Elsevier eBooks · doi:10.1016/b978-0-323-47674-4.00002-5 · Cited by 5
Li, J., Feng, Y., Tan, Y., Duan, Q., & Zhang, Q. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.863560 · Cited by 3
“Whether overall there is a differential response to MET TKIs according to MET amplification status or concurrent other somatic mutations in the context of METex14 alterations need to be investigated in a larger series of patients or clinical trials to find out the underlying mechanism.”
BackgroundTargeting Oncogenic Driver Mutations in Lung Cancer
Lee, M. H., Rous, F. A., Borczuk, A., Liu, S. V., Gadgeel, S. M., & Halmos, B. (2023) · Cambridge University Press eBooks · doi:10.1017/9781009336123 · Cited by 2
Kothari, S., Dusenbery, A. C., Doucette, A. G., Zhang, D. Y., Ballinger, D. G., Desai, A. S., Morrissette, J. J. D., Bagley, S. J., & Nasrallah, M. P. (2023) · Neuro-Oncology Practice · doi:10.1093/nop/npad022 · Cited by 3
Ferreira, M., Swalduz, A., Greillier, L., du Rusquec, P., Curcio, H., Raimbourg, J., Toffart, A., Gounant, V., Couraud, S., Chabot, G. D., et al. (2024) · Lung Cancer · doi:10.1016/j.lungcan.2024.107934 · Cited by 3
Truong, M., Pawlak, G., Meneboo, J., Sebda, S., Fernandes, M., Figeac, M., Elati, M., & Tulasne, D. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-08086-x · Cited by 3
“Such mutations result in in-frame skipping of this exon (METex14Del) [6, 7] and thus deletion of the juxtamembrane regulatory domain of the receptor [8, 9].”
[MET Exon 14 Skipping Mutations in Non-small Cell Lung Cancer].
Yin, L., & Lü, Y. (2018) · Europe PMC (PubMed Central) · doi:10.3779/j.issn.1009-3419.2018.07.09 · Cited by 3
Shah, R., Alex, D., & Xu, Z. (2021) · touchREVIEWS in Oncology & Haematology · doi:10.17925/ohr.2021.16.2.100 · Cited by 3
“However, METex14 skipping is associated with more than 120 reported sequence variants in splice sites, which makes it challenging to detect these mutations using only DNA-based assays.(57,63) Therefore, analysis of RNA transcripts allows for the verification of fusion between exons 13 and 15.”
BackgroundInfluentialShi, M., Ma, J., Feng, M., Liang, L., Chen, H., Wang, T., & Xie, Z. (2021) · Cancer Genetics · doi:10.1016/j.cancergen.2021.04.005 · Cited by 3
Moving molecular subtypes to the clinic in gastric cancer
Chao, J., Lee, J., & Klempner, S. J. (2016) · Translational Cancer Research · doi:10.21037/tcr.2016.05.21 · Cited by 3
“Several large series across cancer types have exemplified the use of large genomic datasets to identify uncommon alterations with significant therapeutic implications (17,18).”
BackgroundMolecular Testing in Lung Cancer
Shiau, C. J., & Tsao, M. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800886-7.00023-6 · Cited by 3
Mazzarella, L. (2018) · ecancermedicalscience · doi:10.3332/ecancer.2018.817 · Cited by 3
Treatment of Patients With Non–Small-Cell Lung Cancer Harboring Rare Oncogenic Mutations
Marmarelis, M. E., & Langer, C. J. (2020) · Clinical Lung Cancer · doi:10.1016/j.cllc.2020.01.010 · Cited by 3
Metadata
- Authors
- Frampton, G. M., Ali, S. M., Rosenzweig, M., Chmielecki, J., Lu, X., Bauer, T. M., Akimov, M., Bufill, J. A., Lee, C., Jentz, D., Hoover, R., Ou, S.-H. I., Salgia, R., Brennan, T., Chalmers, Z. R., Jaeger, S., Huang, A., Elvin, J. A., Erlich, R., Fichtenholtz, A., Gowen, K. A., Greenbowe, J., Johnson, A., Khaira, D., McMahon, C., Sanford, E. M., Roels, S., White, J., Greshock, J., Schlegel, R., Lipson, D., Yelensky, R., Morosini, D., Ross, J. S., Collisson, E., Peters, M., Stephens, P. J., & Miller, V. A.
- Affiliations
- Foundation Medicine (United States) (US)
- University of California, San Francisco (US)
- Tennessee Oncology (US)
- Novartis (Switzerland) (CH)
- 5Michiana Hematology-Oncology, PC, Mishawaka, Indiana.
- University of North Carolina at Chapel Hill (US)
- South Bend Medical Foundation (US)
- University of California, Irvine (US)
- University of Chicago (US)
- 1Foundation Medicine Inc., Cambridge, Massachusetts.
- Corresponding author
- Frampton, Garrett M.
- ORCID
- Frampton, Garrett M.
- Ali, Siraj M.
- Rosenzweig, Mark
- Chmielecki, Juliann
- Lu, Xinyuan
- Bauer, Todd M.
- Akimov, Mikhail
- Lee, Carrie
- Ou, Sai-Hong Ignatius
- Salgia, Ravi
- Chalmers, Zachary R.
- Huang, Alan
- Elvin, Julia A.
- Johnson, Adrienne
- Sanford, Eric M.
- Roels, Steven
- Greshock, Joel
- Lipson, Doron
- Yelensky, Roman
- Ross, Jeffrey S.
- Collisson, Eric
- Miller, Vincent A.
- Venue
- Cancer Discovery
- Published
- 2015-08-01
- Volume
- 5
- Issue
- 8
- Pages
- 850-859
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2160212814
- Cited by
- 796
- References
- 41
- Citations by year
- 2026: 26 · 2025: 47 · 2024: 69 · 2023: 83 · 2022: 73 · 2021: 97 · 2020: 91 · 2019: 71 · 2018: 71 · 2017: 86 · 2016: 65 · 2015: 13
- FWCI
- 62.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P30CA016086)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Mechanisms and Therapy
- Keywords
- MET activation, MET inhibitors, exon skipping, lung adenocarcinoma, glioma, histiocytic sarcoma, targeted therapy sensitivity, oncogenic transformation, comprehensive genomic profiling, tumor genomic profiles
- MeSH terms
- Aged, Aged, 80 and over, Antineoplastic Agents, Exons, Female, Humans, Immunohistochemistry, Male, Mutation, Neoplasm Staging, Neoplasms, Tomography, X-Ray Computed, Cluster Analysis, Alternative Splicing, Drug Resistance, Neoplasm, Proto-Oncogene Proteins c-met, Gene Expression Profiling, Genomics, Protein Kinase Inhibitors
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