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]
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“of these mutations are base substitutions occurring at codon D1010 impairing the splice donor site [53,67].”
BackgroundBahcall, M., Paweletz, C. P., Kuang, Y., Taus, L. J., Sim, T., Kim, N. D., Dholakia, K. H., Lau, C. J., Gokhale, P. C., Chopade, P. R., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-21-0344 · Cited by 38
“MET-targeted therapies are clinically effective in METamplified and MET exon 14 deletion mutant (METex14) non– small cell lung cancers (NSCLCs), but their efficacy is limited by the development of drug resistance.”
BackgroundInfluentialTargeting MET in Non-Small Cell Lung Cancer (NSCLC): A New Old Story?
Spagnolo, C. C., Ciappina, G., Giovannetti, E., Squeri, A., Granata, B., Lazzari, C., Pretelli, G., Pasello, G., & Santarpía, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241210119 · Cited by 36
“Preclinical studies showed that MET blockade was effective only in those harboring MET genomic alterations, while targeting the HGF/MET pathway in tumors with wild type MET had a poor effect on cancer cell proliferation [6,54,55].”
BackgroundGroße, A., Große, C., Rechsteiner, M., & Soltermann, A. (2019) · Diagnostic Pathology · doi:10.1186/s13000-019-0789-1 · Cited by 35
Yang, Y., Jin, X., Li, Q., Chen, Y., Chen, F., Zhang, H., Su, Y., Xiao, Y., Di, G., Jiang, Y., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2207201119 · Cited by 35
Unveiling the Role of HGF/c-Met Signaling in Non-Small Cell Lung Cancer Tumor Microenvironment
Yao, S., Liu, X., Feng, Y., Li, Y., Xiao, X., Han, Y., & Xia, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25169101 · Cited by 33
Standardizing Biomarker Testing for Canadian Patients with Advanced Lung Cancer
Melosky, B. L., Blais, N., Cheema, P. K., Couture, C., Juergens, R. A., Kamel‐Reid, S., Tsao, M., Wheatley‐Price, P., Xu, Z., & Ionescu, D. N. (2018) · Current Oncology · doi:10.3747/co.25.3867 · Cited by 35
Targeting MET in NSCLC: An Ever-Expanding Territory
Han, Y., Yu, Y., Miao, D., Zhou, M., Zhao, J., Shao, Z., Jin, R., Le, X., Li, W., & Xia, Y. (2024) · JTO Clinical and Research Reports · doi:10.1016/j.jtocrr.2023.100630 · Cited by 38
“14 – 16 Elevation of the MET gene copy number (GCN) is caused by gene ampli fi cation on chromosome 7 or polysomy or aneuploidy of chromosome 7.”
BackgroundMutations Preventing Regulated Exon Skipping in MET Cause Osteofibrous Dysplasia
Gray, M. J., Kannus, P., Sharma, S., Neyt, C., Zhang, D., Paria, N., Daniel, P. B., Whetstone, H., Sprenger, H., Hammerschmidt, P., et al. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.11.001 · Cited by 32
“In lung cancer, these variants have been suggested to be probable driver mutations, acting in concert with other oncogenic mutations, to protract ligand-dependent signaling mediated by MET through prolongation of receptor occupancy at the plasma membrane.(10,28) Anecdotal evidence suggests that treatment of individual…”
BackgroundApicella, M., Migliore, C., Capelôa, T., Menegon, S., Cargnelutti, M., Degiuli, M., Sapino, A., Sottile, A., Sarotto, I., Casorzo, L., et al. (2016) · Oncogene · doi:10.1038/onc.2016.283 · Cited by 32
MET gene amplification is a mechanism of resistance to entrectinib in ROS1 + NSCLC
Tyler, L. C., Le, A. T., Chen, N., Nijmeh, H., Bao, L., Wilson, T. R., Chen, D., Simmons, B., Turner, K. M., Perusse, D., et al. (2022) · Thoracic Cancer · doi:10.1111/1759-7714.14656 · Cited by 32
Riedel, R. F., Fassunke, J., Tumbrink, H. L., Scheel, A. H., Heydt, C., Hieggelke, L., Scheffler, M., Heimsoeth, A., Nogová, L., Michels, S. Y. F., et al. (2022) · European Journal of Cancer · doi:10.1016/j.ejca.2022.11.010 · Cited by 34
Evolving roles of MET as a therapeutic target in NSCLC and beyond
Lee, J. B., Shim, J. S. G., & Cho, B. C. (2025) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-025-01051-9 · Cited by 34
“MET ex14 mutations are an independent prognostic factor associated with unfavourable OS in patients with NSCLC 28,40,75 .”
InfluentialTargeted Therapy Approaches for MET Abnormalities in Non-Small Cell Lung Cancer
Garon, E. B., & Brodrick, P. M. (2021) · Drugs · doi:10.1007/s40265-021-01477-2 · Cited by 31
“Further, a comprehensive cancer genome profiling was performed by Frampton et al on over 38,000 tumor specimens from unique patients, 221 of which were found to have METex14 alterations [27].”
Yao, Y., Yang, H., Zhu, B., Wang, S., Pang, J., Wu, X., Xu, Y., Zhang, J., Zhang, J., Ou, Q., et al. (2023) · Respiratory Research · doi:10.1186/s12931-023-02329-1 · Cited by 33
“Approximately 3% of NSCLC patients harbor MET exon 14 skipping alterations (METex14), resulting in decreased MET turnover and extended oncogenic downstream signaling pathways [2, 3].”
BackgroundRecent Advances in Targetable Therapeutics in Metastatic Non-Squamous NSCLC
Bansal, P., Osman, D. I., Gan, G. N., Simon, G. R., & Boumber, Y. (2016) · Frontiers in Oncology · doi:10.3389/fonc.2016.00112 · Cited by 31
“In addition to amplification, MET gene alterations, namely exon 14 internal deletions and mutations, are oncogenic in a small fraction of NSCLC patients (65).”
BackgroundBlanc‐Durand, F., Alameddine, R. S., Iafrate, A. J., Tran‐Thanh, D., Lo, Y., Blais, N., Routy, B., Tehfe, M. A., Leduc, C., Romeo, P., et al. (2020) · The Oncologist · doi:10.1634/theoncologist.2020-0502 · Cited by 30
Investigating open reading frames in known and novel transcripts using ORFanage
Varabyou, A., Erdogdu, B., Salzberg, S. L., & Pertea, M. (2023) · Nature Computational Science · doi:10.1038/s43588-023-00496-1 · Cited by 33
“For example, splicing-induced changes in protein sequences have been associated with cancer development and progression, from activation of proto-oncogenes 27 to genome-wide splicing alteration in certain cancer types 28,29 .”
BackgroundKleczko, E. K., & Heasley, L. E. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0816-y · Cited by 31
Recent advances in the management of non-small cell lung cancer
Shojaee, S., & Nana-Sinkam, P. S. (2017) · F1000Research · doi:10.12688/f1000research.11471.1 · Cited by 29
Baldacci, S., Figeac, M., Antoine, M., Descarpentries, C., Kherrouche, Z., Jamme, P., Copin, M., Tulasne, D., Nanni, I., Beau‐Faller, M., et al. (2019) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2019.09.196 · Cited by 29
Overbeck, T. R., Cron, D. A., Schmitz, K., Rittmeyer, A., Körber, W., Hugo, S., Schnalke, J., Lukat, L., Hugo, T., Hinterthaner, M., et al. (2020) · Translational Lung Cancer Research · doi:10.21037/tlcr-19-339 · Cited by 29
“Originally discovered in small cell lung cancer, MET exon 14 skipping mutations have also been described in 3–6% of adenocarcinoma of the lung and about 1–2% of tumors with other NSCLC histologies (10-14).”
BackgroundAbdallah, H. M., Martinez‐Meehan, D., Lutfi, W., Dhupar, R., Grenda, T. R., Schuchert, M. J., Christie, N. A., Luketich, J. D., & Okusanya, O. T. (2021) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2021.01.081 · Cited by 29
Targeting splicing factors for cancer therapy
Bashari, A., Siegfried, Z., & Karni, R. (2023) · RNA · doi:10.1261/rna.079585.123 · Cited by 31
“506 RNA (2023) 29:506–515; Published by Cold Spring Harbor Laboratory Press for the RNA Society et al. 2013; Supek et al. 2014; Frampton et al. 2015; Jung et al. 2015), or bymisregulation of trans-acting splicing factors (e.g., over- or underexpression, copy-number variation or mutations) that may…”
MethodRecent advances in the management of pulmonary sarcomatoid carcinoma
Shum, E., Stuart, M., Borczuk, A., Wang, F., Cheng, H., & Halmos, B. (2016) · Expert Review of Respiratory Medicine · doi:10.1586/17476348.2016.1157475 · Cited by 29
“Over the last year, multiple other studies reported on MET exon 14 skipping events defining a subset of NSCLCs responsive to MET inhibition and several of these reports also included patients with sarcomatoid lung carcinoma providing immediate validation of these findings [49,50].”
BackgroundDifferential responses of MET activations to MET kinase inhibitor and neutralizing antibody
Kou, J., Musich, P. R., Staal, B., Kang, L., Qin, Y. H., Yao, Z. Q., Zhang, B., Wu, W., Tam, A., Huang, A., et al. (2018) · Journal of Translational Medicine · doi:10.1186/s12967-018-1628-y · Cited by 29
Self-citationTitmarsh, H. F., O’Connor, R. A., Dhaliwal, K., & Akram, A. R. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00054 · Cited by 30
“Case reports from three patients also provides limited clinical data to support this conclusion (8).”
ResultYang, H., Zhou, Z. X., Lin, L. W., Yang, M., Li, C., Li, Z., Yu, X., Lizaso, A., Han‐Zhang, H., Li, B., et al. (2020) · Lung Cancer · doi:10.1016/j.lungcan.2020.08.009 · Cited by 30
Complications following novel therapies for non‐small cell lung cancer
Skribek, M., Rounis, K., Tsakonas, G., & Ekman, S. (2022) · Journal of Internal Medicine · doi:10.1111/joim.13445 · Cited by 28
Kim, S. Y., Yin, J., Bohlman, S., Walker, P., Dacic, S., Kim, C., Khan, H., Liu, S. V., Ma, P. C., Nagasaka, M., et al. (2022) · JTO Clinical and Research Reports · doi:10.1016/j.jtocrr.2022.100381 · Cited by 29
“47% by WTS and the donor splice site base substitutions as the most common alteration leading to a skipped variant.(2,3,9,11,17,32) Approximately 11% of patients with a skipped variant had no associated DNA alteration, which may be secondary to underlying long deletions not captured owing to limitations in detection,…”
BackgroundResultNisa, L., Häfliger, P., Turan, M. P., Giger, R., Francica, P., Aebersold, D. M., Charles, R., Zimmer, Y., & Medová, M. (2017) · Molecular Cancer · doi:10.1186/s12943-017-0660-5 · Cited by 28
Moreno, V., Greil, R., Yachnin, J., Majem, M., Wermke, M., Arkenau, H., Basque, J., Nidamarthy, P. K., Kapoor, S., Cui, X., et al. (2021) · Clinical Therapeutics · doi:10.1016/j.clinthera.2021.04.006 · Cited by 27
Precision oncology: current and future platforms for treatment selection
Tang, X., Berger, M. F., & Solit, D. B. (2024) · Trends in cancer · doi:10.1016/j.trecan.2024.06.009 · Cited by 32
Paasinen-Sohns, A., Koelzer, V. H., Frank, A., Schafroth, J., Gisler, A., Sachs, M., Graber, A., Rothschild, S. I., WICKI, A. N., Cathomas, G., et al. (2017) · Neoplasia · doi:10.1016/j.neo.2017.01.003 · Cited by 27
“MET mutations were also unexpectedly detected in tumor entities such as pancreatic and thyroid cancer that are not routinely submitted for molecular analysis by NGS [33,34,36].”
BackgroundGenova, C., Rossi, G., Tagliamento, M., Rijavec, E., Biello, F., Cerbone, L., Zullo, L., & Grossi, F. (2020) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2020.1714441 · Cited by 27
“detected in 3–4% of lung adenocarcinoma samples [107], while a higher incidence is observed in pulmonary sarcomatoid carcinomas (20–30%) [108,109].”
BackgroundMET exon 14 skipping mutation positive non-small cell lung cancer: Response to systemic therapy
Wong, S. K., Alex, D., Bosdet, I., Hughesman, C. B., Karsan, A., Yip, S. S. F., & Ho, C. (2021) · Lung Cancer · doi:10.1016/j.lungcan.2021.02.030 · Cited by 27
State of the structure address on MET receptor activation by HGF
Linossi, E. M., Estevam, G. O., Oshima, M., Fraser, J. S., Collisson, E. A., & Jura, N. (2021) · Biochemical Society Transactions · doi:10.1042/bst20200394 · Cited by 27
Self-citationCancer Etiology and Prevention Principle: “1 + X”
Liu, H., & Dong, Z. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-1862 · Cited by 29
“MET is frequently overexpressed, activated, and sometimes mutated in lung cancer, which suggests that itmay be a promising target for lung cancer treatment (28).”
BackgroundAl‐Ghabkari, A., Huang, B., & Park, M. (2024) · Cells · doi:10.3390/cells13030218 · Cited by 27
“Consequently, the loss of the direct Cbl TKB-binding site, by loss of exon 14, is associated with reduced ubiquitination, decreased degradation, and sustained Met activation following HGF stimulation, leading to increased oncogenic activity [89,90].”
BackgroundHeydt, C., Becher, A.-K., Wagener‐Ryczek, S., Ball, M., Schultheis, A. M., Schallenberg, S., Rüsseler, V., Büttner, R., & Merkelbach‐Bruse, S. (2019) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2019.09.003 · Cited by 27
Fusion gene and splice variant analyses in liquid biopsies of lung cancer patients
Aguado, C., Giménez-Capitán, A. A., Karachaliou, N., Pérez-Rosado, A., Viteri, S., Morales-Espinosa, D., & Rosell, R. (2016) · Translational Lung Cancer Research · doi:10.21037/tlcr.2016.09.02 · Cited by 26
“In vitro preclinical studies indicated that MET-targeted agents can counteract oncogenesis resulting from MET exon 14 loss and the efficacy of these agents in NSCLC patients with MET 14 positive tumors has recently been demonstrated (50,54).”
BackgroundHughes, V. S., & Siemann, D. W. (2019) · Oncotarget · doi:10.18632/oncotarget.26546 · Cited by 26
“com This occurs in 3–4% of non-small cell lung cancer (NSCLC) patients, and less frequently in other common forms of cancer [16].”
BackgroundTargeted Therapy for Non-Small Cell Lung Cancer
Noor, Z. S., Cummings, A. L., Johnson, M. M., Spiegel, M. L., & Goldman, J. W. (2020) · Seminars in Respiratory and Critical Care Medicine · doi:10.1055/s-0039-1700994 · Cited by 27
Biological Aspects of Cancer Health Disparities
Freedman, J. A., Abo, M. A., Allen, T. A., Piwarski, S. A., Wegermann, K., & Patierno, S. R. (2021) · Annual Review of Medicine · doi:10.1146/annurev-med-070119-120305 · Cited by 26
Stencel, K. M., Chmielewska, I., Milanowski, J., & Ramlau, R. (2021) · Cancers · doi:10.3390/cancers13081829 · Cited by 27
“eration of neoplastic cells, their longevity, invasiveness and ability to metastasize [21,22].”
BackgroundLiquid biopsy as an option for predictive testing and prognosis in patients with lung cancer
Qvick, A., Stenmark, B., Carlsson, J., Isaksson, J., Karlsson, C., & Helenius, G. (2021) · Molecular Medicine · doi:10.1186/s10020-021-00331-1 · Cited by 27
Friese‐Hamim, M., Clark, A., Perrin, D., Crowley, L., Reusch, C., Bogatyrova, O., Zhang, H., Crandall, T., Lin, J., Ma, J., et al. (2021) · Lung Cancer · doi:10.1016/j.lungcan.2021.11.020 · Cited by 26
Wang, A., Yang, W. H., Li, Y., Zhang, Y., Zhou, J., Zhang, R., Zhang, W., Zhu, J., Zeng, Y., Liu, Z., et al. (2022) · Cell Communication and Signaling · doi:10.1186/s12964-021-00818-8 · Cited by 26
“MET exon 14 skipping mutation (METex14), an oncogenic driver in approximately 3–4% of NSCLCs [42, 43], and MET amplification, found in 20% of EGFR-TKI-resistant NSCLC patients [44, 45], are often detected and frequently studied in NSCLC.”
BackgroundCagle, P. T., Sholl, L. M., Lindeman, N. I., Alsabeh, R., Divaris, D. X. G., Foulis, P., Lee, G., Neal, J. W., Nowak, J. A., Yu, P. P., et al. (2013) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2013-0232-cp · Cited by 25
“Recently, splicing variants and insertion-deletion mutations leading to MET exon 14 deletion have been found in about 3% of lung adenocarcinomas; these events lead to MET activation and are associated with response to crizotinib and cabozantinib.(31,32) MET amplification can be seen in tumors with MET exon 14 deletion.”
BackgroundSunami, K., Furuta, K., Tsuta, K., Sasada, S., Izumo, T., Nakaoku, T., Shimada, Y., Saito, M., Nokihara, H., WATANABE, S.-I. I., et al. (2015) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2015.10.005 · Cited by 25
“The present study also focused on MET exon 14 skipping, a novel druggable aberration that is being examined in clinical trials as a therapeutic target.(18,19)”
BackgroundSalgia, R. (2016) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2016.1181545 · Cited by 25
“of lung adenocarcinomas and in 1–2% of other NSCLC subsets [61,62], and respond to MET inhibitors such as crizotinib, cabozantinib, and capmatinib (INC280) [61–63].”
BackgroundSelf-citationc-Met kinase inhibitors: an update patent review (2014-2017)
Zhang, Q.-W., Ye, Z.-D., & Shi, L. (2018) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2019.1552261 · Cited by 25
Sakai, H., Morise, M., Kato, T., Matsumoto, S., Sakamoto, T., Kumagai, T., Tokito, T., Atagi, S., Kozuki, T., Tanaka, H., et al. (2021) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyab072 · Cited by 25
An updated patent review of small-molecule c-Met kinase inhibitors (2018-present)
Chu, C., Rao, Z., Pan, Q., & Zhu, W. (2021) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2022.2008356 · Cited by 25
MET in Non-Small-Cell Lung Cancer (NSCLC): Cross ‘a Long and Winding Road’ Looking for a Target
Spitaleri, G., Aliaga, P. T., Attili, I., Signore, E. D., Corvaja, C., Corti, C., Uliano, J., Passaro, A., & de Marinis, F. (2023) · Cancers · doi:10.3390/cancers15194779 · Cited by 24
“%) cases with METex14: 3.0% in lung adenocarcinoma and 2.3% in non-adenocarcinoma lung cancers [35].”
BackgroundInfluential
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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