Activation of MET via Diverse Exon 14 Splicing Alterations Occurs in Multiple Tumor Types and Confers Clinical Sensitivity to MET Inhibitors

Frampton, Garrett M.; Ali, Siraj M.; Rosenzweig, Mark; Chmielecki, Juliann; Lu, Xinyuan; Bauer, Todd M.; Akimov, Mikhail; Bufill, Jose A.; Lee, Carrie; Jentz, David; Hoover, Rick; Ou, Sai-Hong Ignatius; Salgia, Ravi; Brennan, Tim; Chalmers, Zachary R.; Jaeger, Savina; Huang, Alan; Elvin, Julia A.; Erlich, Rachel; Fichtenholtz, Alex; Gowen, Kyle A.; Greenbowe, Joel; Johnson, Adrienne; Khaira, Depinder; McMahon, Caitlin; Sanford, Eric M.; Roels, Steven; White, Jared; Greshock, Joel; Schlegel, Robert; Lipson, Doron; Yelensky, Roman; Morosini, Deborah; Ross, Jeffrey S.; Collisson, Eric; Peters, Malte; Stephens, Philip J.; Miller, Vincent A.

doi:10.1158/2159-8290.cd-15-0285

Cited by 800Lung Cancer Treatments and MutationsCancer Genomics and DiagnosticsCancer Mechanisms and Therapy

Activation of MET via Diverse Exon 14 Splicing Alterations Occurs in Multiple Tumor Types and Confers Clinical Sensitivity to MET Inhibitors

Frampton, Garrett M., Ali, Siraj M., Rosenzweig, Mark, Chmielecki, Juliann, Lu, Xinyuan, Bauer, Todd M., Akimov, Mikhail, Bufill, Jose A. +30 more·2015·Cancer Discovery

DOI 10.1158/2159-8290.cd-15-0285

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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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Large-scale profiling studies in NSCLC have revealed multiple non-random patterns of co-occurring or mutually exclusive mutations, which typically vary depending on the particular oncogenic driver mutation.
“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]
Landmark large scale sequencing studies have established a census of major KRAS co-mutations in both early-stage and advanced LUAD.
“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]
The overwhelming majority of EGFR-mutant lung tumors harbor one or more co-mutations, even when analysis is limited to pre-defined sets of cancer-relevant genes within established panels.
“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]
EGFR-mutant LUAD show significant enrichment of NKX2-1 amplification.
“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]
WNT signaling has a central role in LUAD metastasis.
“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]

PIK3CA mutations are preferentially found in advanced-stage tumors.
“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]
ALK-rearranged LUAD are less likely to harbor TP53 alterations (23.8%-26.5%) than other driver subgroups.
“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]
EGFR and CTNNB1 co-mutated NSCLC cells show increased invasive potential in vitro.
“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]
PIK3CA kinase and helical domain mutations occur in 9%-12.4% of advanced-stage EGFR-mutant LUAD.
“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]
Activating CTNNB1 mutations are among the most consistently co-selected alterations in EGFR-mutant LUAD across studies.
“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]
CDKN2A alterations are enriched in advanced-stage LUAD with ALK rearrangement, at 32.5%.
“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]
CDKN2B alterations are enriched in advanced-stage ALK-rearranged LUAD, at 26.5%.
“and CDKN2B (26.5%)”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [15]
CTNNB1 mutation prevalence rises in late-stage EGFR-mutant LUAD to 5.3%-9.6%.
“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]
MET exon 14 skipping LUAD show highly significant enrichment of MDM2 and CDK4 amplification (41.6%) compared with other driver oncogenes.
“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]
RET fusion-positive LUAD have high concurrent CDKN2A loss (29.8%).
“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]
ROS1 fusion-positive LUAD have high concurrent CDKN2B loss (17.7%).
“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]
BRAF-mutant NSCLC co-alteration spectrum mirrors background frequency for TP53, LKB1, ATM, NF1, PIK3CA, KEAP1, MYC, and NKX2-1.
“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]
ERBB2-mutant NSCLC have frequent RB1 mutations (8.9%).
“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 MET exon 14 skipping LUAD, CDKN2A loss (24.1%) and CDKN2B loss (17.5%) occur at rates comparable to the overall NSCLC population.
“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]
ROS1 fusion-positive LUAD have high concurrent CDKN2A loss (30.4%).
“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]
RET- and ROS1-rearranged tumors show a modestly greater TP53 mutation frequency than ALK-rearranged tumors (34.6%-45.5% for RET, 45.6% for ROS1).
“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]
NKX2-1 (19.4%) and ERBB2 itself (14.4%) are preferentially amplified in ERBB2-mutant NSCLC.
“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]
MET exon 14 skipping LUAD show amplification of MET itself.
“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]
RET fusion-positive LUAD have high concurrent CDKN2B loss (25%).
“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]
RET and ROS1 fusion-positive LUAD have relative paucity of TP53 mutations.
“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]
ERBB2-mutant NSCLC have co-mutation frequencies for TP53, CDKN2A, CDKN2B, PIK3CA, CTNNB1, and MDM2 amplification similar to overall NSCLC.
“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]
MET exon 14 skipping LUAD have under-represented TP53 mutations (33.57%).
“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]
RB1, MDM2, CDKN2A (16.6%), and CDKN2B (11.2%) alterations are less common in BRAF-mutant NSCLC.
“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]

Comprehensive molecular profiling of lung adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13385 · Cited by 5,732 · see citing works
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 · see citing works
Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing
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 · see citing works
Self-citation
Mapping 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 · see citing works
Self-citation
Structure Based Drug Design of Crizotinib (PF-02341066), a Potent and Selective Dual Inhibitor of Mesenchymal–Epithelial Transition Factor (c-MET) Kinase and Anaplastic Lymphoma Kinase (ALK)
Cui, 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 953 · see citing works
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 · see citing works
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 589 · see citing works
Functional Expression and Mutations of c-Met and Its Therapeutic Inhibition with SU11274 and Small Interfering RNA in Non–Small Cell Lung Cancer
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 · see citing works
Self-citation
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 · see citing works
Randomized Phase II Trial of Onartuzumab in Combination With Erlotinib in Patients With Advanced Non–Small-Cell Lung Cancer
Spigel, 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 479 · see citing works
Mutation of the c-Cbl TKB Domain Binding Site on the Met Receptor Tyrosine Kinase Converts It into a Transforming Protein
Peschard, P., Fournier, T. M., Lamorte, L., Naujokas, M. A., Band, H., Langdon, W. Y., & Park, M. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00378-1 · Cited by 462 · see citing works
Phase II and Biomarker Study of the Dual MET/VEGFR2 Inhibitor Foretinib in Patients With Papillary Renal Cell Carcinoma
Choueiri, T. K., Vaishampayan, U. N., Rosenberg, J. E., Logan, T. F., Harzstark, A. L., Bukowski, R. M., Rini, B. I., Srinivas, S., Stein, M. N., Adams, L. M., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.43.3383 · Cited by 462 · see citing works
c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions.
Ma, P. C., Kijima, T., Maulik, G., Fox, E. A., Sattler, M., Griffin, J. D., Johnson, B. E., & Salgia, R. (2003) · PubMed · Cited by 454 · see citing works
Self-citation
Activity of Crizotinib (PF02341066), a Dual Mesenchymal-Epithelial Transition (MET) and Anaplastic Lymphoma Kinase (ALK) Inhibitor, in a Non-small Cell Lung Cancer Patient with De Novo MET Amplification
Ou, S. I., Kwak, E. L., Siwak, C. T., Dy, J., Bergethon, K. E., Clark, J. W., Camidge, D. R., Solomon, B., Maki, R. G., Bang, Y., et al. (2011) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31821528d3 · Cited by 435 · see citing works
Self-citation
MET Amplification Identifies a Small and Aggressive Subgroup of Esophagogastric Adenocarcinoma With Evidence of Responsiveness to Crizotinib
Lennerz, J. K., Kwak, E. L., Ackerman, A., Michael, M., Fox, S. B., Bergethon, K. E., Lauwers, G. Y., Christensen, J. G., Wilner, K. D., Haber, D. A., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.35.4928 · Cited by 433 · see citing works
Self-citation
The Genetic Basis for Cancer Treatment Decisions
Dancey, J. E., Bedard, P. L., Onetto-Pothier, N., & Hudson, T. J. (2012) · Cell · doi:10.1016/j.cell.2012.01.014 · Cited by 342 · see citing works
Activation of MET by Gene Amplification or by Splice Mutations Deleting the Juxtamembrane Domain in Primary Resected Lung Cancers
Onozato, R., Kosaka, T., Kuwano, H., Sekido, Y., Yatabe, Y., & Mitsudomi, T. (2009) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3181913e0e · Cited by 326 · see citing works
The Met tyrosine kinase receptor in development and cancer
Gentile, A., Trusolino, L., & Comoglio, P. M. (2008) · Cancer and Metastasis Reviews · doi:10.1007/s10555-007-9107-6 · Cited by 319 · see citing works
A Novel Kinase Inhibitor, INCB28060, Blocks c-MET–Dependent Signaling, Neoplastic Activities, and Cross-Talk with EGFR and HER-3
Liu, X., Wang, Q., Yang, G., Marando, C. A., Koblish, H. K., Hall, L. M., Fridman, J. S., Behshad, E., Wynn, R., Li, Y., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1157 · Cited by 268 · see citing works
Targeting Receptor Tyrosine Kinase MET in Cancer: Small Molecule Inhibitors and Clinical Progress
Cui, J. J. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm401427c · Cited by 216 · see citing works
Met/Hepatocyte Growth Factor Receptor Ubiquitination Suppresses Transformation and Is Required for Hrs Phosphorylation
Abella, J. V., Peschard, P., Naujokas, M. A., Lin, T., Saucier, C., Urbé, S., & Park, M. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9632-9645.2005 · Cited by 203 · see citing works
Met gene copy number predicts the prognosis for completely resected non‐small cell lung cancer
Okuda, K., Sasaki, H., Yukiue, H., Yano, M., & Fujii, Y. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2008.00916.x · Cited by 198 · see citing works
Chipping away at the lung cancer genome
Pao, W. J., & Hutchinson, K. E. (2012) · Nature Medicine · doi:10.1038/nm.2697 · Cited by 192 · see citing works
Transcriptome meta-analysis of lung cancer reveals recurrent aberrations in NRG1 and Hippo pathway genes
Dhanasekaran, S. M., Balbin, O. A., Chen, G., Nadal, E., Sundaram, S. K., Pan, J., Veeneman, B. A., Cao, X., Malik, R., Vats, P., et al. (2014) · Nature Communications · doi:10.1038/ncomms6893 · Cited by 154 · see citing works
LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition
Mahoney, C., Choudhury, B., Davies, H. R., Edkins, S., Greenman, C., van Haaften, G. W., Mironenko, T., Santarius, T., Stevens, C., Stratton, M. R., et al. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6604886 · Cited by 128 · see citing works
Rapid Radiographic and Clinical Improvement After Treatment of a MET-Amplified Recurrent Glioblastoma With a Mesenchymal-Epithelial Transition Inhibitor
Chi, A. S., Batchelor, T. T., Kwak, E. L., Clark, J. W., Wang, D. L., Wilner, K. D., Louis, D. N., & Iafrate, A. J. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.38.4586 · Cited by 110 · see citing works
Durable Complete Response of Metastatic Gastric Cancer with Anti-Met Therapy Followed by Resistance at Recurrence
Catenacci, D. V. T., Henderson, L., Xiao, S., Patel, P. H., Yauch, R. L., Hegde, P. S., Zha, J., Pandita, A., Peterson, A., & Salgia, R. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0175 · Cited by 109 · see citing works
Self-citation
Autocrine CSF-1R activation promotes Src-dependent disruption of mammary epithelial architecture
Wrobel, C. N., Debnath, J., Lin, E., Beausoleil, S. A., Roussel, M. F., & Brugge, J. S. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200309102 · Cited by 107 · see citing works
Response to Crizotinib in a Patient With Lung Adenocarcinoma Harboring a MET Splice Site Mutation
Jenkins, R. W., Oxnard, G. R., Elkin, S. K., Sullivan, E. K., Carter, J. L., & Barbie, D. A. (2015) · Clinical Lung Cancer · doi:10.1016/j.cllc.2015.01.009 · Cited by 103 · see citing works
LKB1 Loss Induces Characteristic Patterns of Gene Expression in Human Tumors Associated with NRF2 Activation and Attenuation of PI3K-AKT
Kaufman, J. M., Amann, J. M., Park, K., Arasada, R. R., Li, H., Shyr, Y., & Carbone, D. P. (2014) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000173 · Cited by 87 · see citing works
MET Mutation Associated with Responsiveness to Crizotinib
Waqar, S. N., Morgensztern, D., & Sehn, J. K. (2015) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000478 · Cited by 83 · see citing works
Evaluation of MET pathway biomarkers in a phase II study of rilotumumab (R, AMG 102) or placebo (P) in combination with epirubicin, cisplatin, and capecitabine (ECX) in patients (pts) with locally advanced or metastatic gastric (G) or esophagogastric junction (EGJ) cancer.
Oliner, K. S., Tang, R., Anderson, A., Lan, Y., Iveson, T. J., Donehower, R. C., Jiang, Y., Dubey, S., & Loh, E. Y. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.30.15_suppl.4005 · Cited by 83 · see citing works
Loss of the exon encoding the juxtamembrane domain is essential for the oncogenic activation of TPR-MET
Vigna, E., Gramaglia, D., Longati, P., Bardelli, A., & Comoglio, P. M. (1999) · Oncogene · doi:10.1038/sj.onc.1202791 · Cited by 81 · see citing works
Gastric cancer cell line Hs746T harbors a splice site mutation of c-Met causing juxtamembrane domain deletion
Asaoka, Y., Tada, M., Ikenoue, T., Seto, M., Imai, M., Miyabayashi, K., Yamamoto, K., Yamamoto, S., Kudo, Y., Mohri, D., et al. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.03.120 · Cited by 78 · see citing works
Cbl-independent degradation of Met: ways to avoid agonism of bivalent Met-targeting antibody
Lee, J. M., Kim, B., Lee, S. B., Jeong, Y., Oh, Y. M., Song, Y.-J., Jung, S. H., Choi, J., Lee, S., Cheong, K. H., et al. (2012) · Oncogene · doi:10.1038/onc.2012.551 · Cited by 74 · see citing works
Identification of a novel type of alternative splicing of a tyrosine kinase receptor. Juxtamembrane deletion of the c-met protein kinase C serine phosphorylation regulatory site.
Lee, C. C., & Yamada, K. M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32190-7 · Cited by 69 · see citing works
Self-citation
MET-Mutated NSCLC with Major Response to Crizotinib
Mendenhall, M. A., & Goldman, J. W. (2015) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000491 · Cited by 60 · see citing works
An alternatively spliced form of Met receptor is tumorigenic
Lee, J., Gao, C. F., Lee, C. C., Kim, M. D., & Woude, G. F. V. (2006) · Experimental & Molecular Medicine · doi:10.1038/emm.2006.66 · Cited by 54 · see citing works
Self-citation
Phase I study of the safety and efficacy of INC280 in patients with advanced MET-dependent solid tumors.
Bang, Y., Su, W., Nam, D., Lim, W., Bauer, T. M., Braña, I., Poon, R. T. P., Hong, D. S., Lin, C., Peng, B., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.2520 · Cited by 45 · see citing works
Self-citation
Durable Response to Crizotinib in a MET-Amplified, KRAS-Mutated Carcinoma of Unknown Primary
Palma, N. A., Ali, S. M., O'Connor, J., Dutta, D., Wang, K., Soman, S., Palmer, G. A., Morosini, D., Ross, J. S., Lipson, D., et al. (2014) · Case Reports in Oncology · doi:10.1159/000365326 · Cited by 33 · see citing works
Self-citation
Identification of MET genomic amplification, protein expression and alternative splice isoforms in neuroblastomas
Yan, B., Lim, M., Zhou, L., Kuick, C. H., Leong, M. Y., Yong, K. J., Aung, L. O., Salto‐Tellez, M., & Chang, K. T. E. (2013) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2012-201375 · Cited by 18 · see citing works

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The biology and management of non-small cell lung cancer
Herbst, R. S., Morgensztern, D., & Boshoff, C. (2018) · Nature · doi:10.1038/nature25183 · Cited by 4,891 · see citing works
OncoKB: A Precision Oncology Knowledge Base
Chakravarty, D., Gao, J., Phillips, S. M., Kundra, R., Zhang, H., Wang, J., Rudolph, J. E., Yaeger, R. D., Soumerai, T. E., Nissan, M. H., et al. (2017) · JCO Precision Oncology · doi:10.1200/po.17.00011 · Cited by 2,735 · see citing works
“However, durable complete or partial responses to crizotinib and cabozantinib in patients with MET exon 14 altered lung cancers have been reported 15,19 .”
Background
Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Planchard, D., Popat, S., Kerr, K., Novello, S., Smit, E. F., Faivre-Finn, C., Mok, T. S., Reck, M., Van Schil, P. E., Hellmann, M. D., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy275 · Cited by 2,274 · see citing works
Small molecules in targeted cancer therapy: advances, challenges, and future perspectives
Zhong, L., Li, Y., Xiong, L., Wang, W., Wu, M., Yuan, T., Yang, W. M., Tian, C., Miao, Z., Wang, T., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00572-w · Cited by 1,735 · see citing works
Non–Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology
Ettinger, D. S., Wood, D. E., Aisner, D. L., Akerley, W., Bauman, J. R., Bharat, A., Bruno, D. S., Chang, J. Y., Chirieac, L. R., D’Amico, T. A., et al. (2022) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2022.0025 · Cited by 1,405 · see citing works
Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy
Skoulidis, F., & Heymach, J. V. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0179-8 · Cited by 1,019 · see citing works
Capmatinib in MET Exon 14–Mutated or MET -Amplified Non–Small-Cell Lung Cancer
Wolf, J., Seto, T., Han, J., Reguart, N., Garon, E. B., Groen, H. J. M., Tan, D. S. W., Hida, T., de Jonge, M. J. A., Orlov, S., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2002787 · Cited by 1,004 · see citing works
Self-citation
Understanding and targeting resistance mechanisms in NSCLC
Rotow, J. K., & Bivona, T. G. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.84 · Cited by 978 · see citing works
Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology
Lindeman, N. I., Cagle, P. T., Aisner, D. L., Arcila, M. E., Beasley, M. B., Bernicker, E., Colasacco, C., Đačić, S., Hirsch, F. R., Kerr, K. M., et al. (2018) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2017-0388-cp · Cited by 959 · see citing works
Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients
Kahles, A., Lehmann, K.-V., Toussaint, N. C., Hüser, M., Stark, S. G., Sachsenberg, T. T., Stegle, O., Kohlbacher, O., Sander, C., Johnson, R., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.07.001 · Cited by 891 · see citing works
“A prominent example for cis-acting mutations is found in the splice junctions ofMET leading to skipping of exon 14, resulting in activation of MET but also providing specific sensitivity to MET inhibitors (Frampton et al., 2015; Paik et al., 2015).”
Background
Non–Small Cell Lung Cancer, Version 4.2024
Riely, G. J., Wood, D. E., Ettinger, D. S., Aisner, D. L., Akerley, W., Bauman, J. R., Bharat, A., Bruno, D. S., Chang, J. Y., Chirieac, L. R., et al. (2024) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2204.0023 · Cited by 897 · see citing works
Tepotinib in Non–Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations
Paik, P. K., Felip, E., Veillon, R., Sakai, H., Cortot, A. B., Garassino, M. C., Mazières, J., Viteri, S., Senellart, H., van Meerbeeck, J. P., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2004407 · Cited by 887 · see citing works
Roles and mechanisms of alternative splicing in cancer — implications for care
Bonnal, S., López‐Oreja, I., & Valcárcel, J. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0350-x · Cited by 741 · see citing works
MET Exon 14 Mutations in Non–Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression
Awad, M. M., Oxnard, G. R., Jackman, D. M., Savukoski, D. O., Hall, D., Shivdasani, P., Heng, J. C., Dahlberg, S. E., Janne, P. A., Verma, S., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.63.4600 · Cited by 697 · see citing works
Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors
Lindeman, N. I., Cagle, P. T., Aisner, D. L., Arcila, M. E., Beasley, M. B., Bernicker, E., Colasacco, C., Đačić, S., Hirsch, F. R., Kerr, K. M., et al. (2018) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2017.12.001 · Cited by 660 · see citing works
The emerging clinical relevance of genomics in cancer medicine
Berger, M. F., & Mardis, E. R. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0002-6 · Cited by 627 · see citing works
RNA splicing dysregulation and the hallmarks of cancer
Bradley, R. K., & Anczuków, O. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-022-00541-7 · Cited by 579 · see citing works
Molecular targeted therapy for anticancer treatment
Min, H.-Y., & Lee, H.-Y. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00864-3 · Cited by 569 · see citing works
The Functional Impact of Alternative Splicing in Cancer
Climente-González, H., Porta‐Pardo, E., Godzik, A., & Eyras, E. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.012 · Cited by 546 · see citing works
Implementing Genome-Driven Oncology
Hyman, D. M., Taylor, B. S., & Baselga, J. M. (2017) · Cell · doi:10.1016/j.cell.2016.12.015 · Cited by 505 · see citing works
Aberrant RNA splicing in cancer; expression changes and driver mutations of splicing factor genes
Sveen, A., Kilpinen, S. K., Ruusulehto, A., Lothe, R. A., & Skotheim, R. I. (2015) · Oncogene · doi:10.1038/onc.2015.318 · Cited by 463 · see citing works
Tyrosine kinase inhibitors for solid tumors in the past 20 years (2001–2020)
Huang, L., Jiang, S., & Shi, Y. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00977-0 · Cited by 467 · see citing works
Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration
Drilon, A. E. D. C., Clark, J. W., Weiss, J. M., Ou, S. I., Camidge, D. R., Solomon, B., Otterson, G. A., Villaruz, L. C., Riely, G. J., Heist, R. S., et al. (2020) · Nature Medicine · doi:10.1038/s41591-019-0716-8 · Cited by 396 · see citing works
Self-citation
Targeting MET in Lung Cancer: Will Expectations Finally Be MET?
Drilon, A. E. D. C., Cappuzzo, F., Ou, S. I., & Camidge, D. R. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.10.014 · Cited by 393 · see citing works
“The reported prevalence of de novo MET amplification in NSCLC ranges from 1% to 5%, depending on the level of preselection, the assay, and the positivity cutpoint used (see Table 1).(27,29,35,36,53) In adenocarcinoma, because most true oncogenic drivers are mutually exclusive, so-called oncogene overlap analysis was u…”
BackgroundMethodInfluentialSelf-citation
Characterization of 298 Patients with Lung Cancer Harboring MET Exon 14 Skipping Alterations
Schrock, A. B., Frampton, G. M., Suh, J. H., Chalmers, Z. R., Rosenzweig, M. R., Erlich, R., Halmos, B., Goldman, J. W., Forde, P. M., Leuenberger, K., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.06.004 · Cited by 386 · see citing works
Self-citation
Known and novel roles of the MET oncogene in cancer: a coherent approach to targeted therapy
Comoglio, P. M., Trusolino, L., & Boccaccio, C. (2018) · Nature reviews. Cancer · doi:10.1038/s41568-018-0002-y · Cited by 380 · see citing works
Clinical and analytical validation of FoundationOne®CDx, a comprehensive genomic profiling assay for solid tumors
Milbury, C. A., Creeden, J., Yip, W., Smith, D. L., Pattani, V. P., Maxwell, K., Sawchyn, B., Gjoerup, O. V., Meng, W., Skoletsky, J., et al. (2022) · PLoS ONE · doi:10.1371/journal.pone.0264138 · Cited by 384 · see citing works
Self-citation
EGFR signaling pathway as therapeutic target in human cancers
Levantini, E., Maroni, G., Re, M. D., & Tenen, D. G. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.04.002 · Cited by 372 · see citing works
Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors
Lindeman, N. I., Cagle, P. T., Aisner, D. L., Arcila, M. E., Beasley, M. B., Bernicker, E., Colasacco, C., Đačić, S., Hirsch, F. R., Kerr, K. M., et al. (2018) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2017.11.004 · Cited by 348 · see citing works
Mutational Landscape of Secondary Glioblastoma Guides MET-Targeted Trial in Brain Tumor
Hu, H., Mu, Q., Bao, Z., Chen, Y., Liu, Y., Chen, J., Wang, K., Wang, Z., Nam, Y., Jiang, B., et al. (2018) · Cell · doi:10.1016/j.cell.2018.09.038 · Cited by 343 · see citing works
“Therefore, METex14 results in prolonged stability and constitutive activation of MET (Frampton et al., 2015) (Figure 2B).”
Phase Ib/II Study of Capmatinib (INC280) Plus Gefitinib After Failure of Epidermal Growth Factor Receptor (EGFR) Inhibitor Therapy in Patients With EGFR -Mutated, MET Factor–Dysregulated Non–Small-Cell Lung Cancer
Wu, Y.-L., Zhang, L., Kim, D.-W., Liu, X., Lee, D. H., Yang, J. C.-H., Ahn, M.-J., Vansteenkiste, J. F., Su, W.-C., Felip, E., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.77.7326 · Cited by 333 · see citing works
Self-citation
Results From the Phase III Randomized Trial of Onartuzumab Plus Erlotinib Versus Erlotinib in Previously Treated Stage IIIB or IV Non–Small-Cell Lung Cancer: METLung
Spigel, D. R., Edelman, M. J., O'Byrne, K. J., Paz-Ares, L. G., Mocci, S., Phan, S. C., Shames, D. S., Smith, D., Yu, W., Paton, V. E., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.69.2160 · Cited by 332 · see citing works
MET-dependent solid tumours — molecular diagnosis and targeted therapy
Guo, R., Luo, J., Chang, J. C., Rekhtman, N., Arcila, M. E., & Drilon, A. E. D. C. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0377-z · Cited by 329 · see citing works
PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers
Sabari, J. K., Leonardi, G. C., Shu, C. A., Umeton, R., Montecalvo, J., Ni, A., Chen, R., Dienstag, J., Mrad, C., Bergagnini, I., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy334 · Cited by 321 · see citing works
Aberrant RNA Splicing in Cancer
Escobar‐Hoyos, L. F., Knorr, K. L. B., & Abdel-Wahab, O. I. (2018) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030617-050407 · Cited by 300 · see citing works
“MET exon 14 alterations have been detected in a variety of cancers and confer sensitivity to MET inhibitors (Frampton et al. 2015).”
Background
Lung cancer in patients who have never smoked — an emerging disease
LoPiccolo, J., Gusev, A., Christiani, D. C., & Janne, P. A. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00844-0 · Cited by 307 · see citing works
“80,105–108 and/or MET amplifications (prevalence of 1–6%, varying based on MET copy number) 109–111 .”
Diagnosis and Molecular Classification of Lung Cancer
Rodriguez‐Canales, J., Parra-Cuentas, E. R., & Wistuba, I. I. (2016) · Cancer treatment and research · doi:10.1007/978-3-319-40389-2_2 · Cited by 277 · see citing works
“Importantly, in vitro tests showed sensitivity to MET inhibitors in cells harboring METex14 alterations and patients whose tumors harbored these alterations derived meaningful clinical benefit from MET inhibitors [83].”
BackgroundInfluential
Recent developments of c‐Met as a therapeutic target in hepatocellular carcinoma
Bouattour, M., Raymond, É., Qin, S., Cheng, A., Stammberger, U. M., Locatelli, G., & Faivre, S. J. (2017) · Hepatology · doi:10.1002/hep.29496 · Cited by 260 · see citing works
“1%.((78)) Other activating MET mutations are also rare, detectable only in childhood HCCs((79)); and most HCCs that express high levels of c-Met receptor have neither amplified nor mutated MET.”
Background
Hepatocyte growth factor/ MET in cancer progression and biomarker discovery
Matsumoto, K., Umitsu, M., Silva, D. M. D., Roy, A., & Bottaro, D. P. (2017) · Cancer Science · doi:10.1111/cas.13156 · Cited by 238 · see citing works
Targeting c-MET in gastrointestinal tumours: rationale, opportunities and challenges
Bradley, C. A., Salto‐Tellez, M., Laurent‐Puig, P., Bardelli, A., Rolfo, C. D., Tabernero, J. M., Khawaja, H. A., Lawler, M., Johnston, P. G., & Schaeybroeck, S. V. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.40 · Cited by 227 · see citing works
Molecular Mechanisms of Acquired Resistance to MET Tyrosine Kinase Inhibitors in Patients with MET Exon 14–Mutant NSCLC
Recondo, G., Bahcall, M., Spurr, L. F., Che, J., Ricciuti, B., Leonardi, G. C., Lo, Y., Li, Y. Y., Lamberti, G., Nguyen, T. T., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-3608 · Cited by 226 · see citing works
Targeting MET Dysregulation in Cancer
Recondo, G., Che, J., Janne, P. A., & Awad, M. M. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-1446 · Cited by 230 · see citing works
“De novo MET exon 14 alterations are almost always mutually exclusive with other oncogenic driver mutations like KRAS, EGFR, ALK, ROS1, and RET (16,24), and commonly co-occurring genomic alterations include mutations in TP53, loss of CDKN2A/B, and amplifications of MET, MDM2, and CDK4/6 (16,24,26).”
BackgroundInfluential
HGF/c-MET pathway in cancer: from molecular characterization to clinical evidence
Fu, J., Su, X., Li, Z., Deng, L., Liu, X., Feng, X., & Peng, J. (2021) · Oncogene · doi:10.1038/s41388-021-01863-w · Cited by 235 · see citing works
Drug resistance to targeted therapeutic strategies in non-small cell lung cancer
Liu, W., Du, Y., Wen, R. M., Yang, M., & Xu, J. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.107438 · Cited by 218 · see citing works
A method of high-throughput functional evaluation of EGFR gene variants of unknown significance in cancer
Kohsaka, S., Nagano, M., Ueno, T., Suehara, Y., Hayashi, T., Shimada, N., Takahashi, K., Suzuki, K., Takamochi, K., Takahashi, F., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aan6566 · Cited by 210 · see citing works
Precision medicine in non-small cell lung cancer: Current applications and future directions
Yang, S., Schultheis, A. M., Yu, H. A., Mandelker, D. L., Ladanyi, M., & Büttner, R. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.07.009 · Cited by 216 · see citing works
HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium
Pillai, R. N., Behera, M., Berry, L. D., Rossi, M. R., Kris, M. G., Johnson, B. E., Bunn, P. A., Ramalingam, S. S., & Khuri, F. R. (2017) · Cancer · doi:10.1002/cncr.30869 · Cited by 211 · see citing works
“Recently, an exon splicing mutation in the MET gene was found in nearly 4% of patients, causing prolonged stability of the MET protein due to loss of the ubiquitin-binding domain needed for protein degradation.(36) This group appears to benefit from MET inhibitors, as was observed in 3 patients who responded to MET in…”
Background
Genomic Profiling of Advanced Non–Small Cell Lung Cancer in Community Settings: Gaps and Opportunities
Gutierrez, M. E., Choi, K., Lanman, R. B., Licitra, E. J., Skrzypczak, S. M., Benito, R. P., Wu, T., Arunajadai, S. G., Kaur, S., Harper, H. D., et al. (2017) · Clinical Lung Cancer · doi:10.1016/j.cllc.2017.04.004 · Cited by 206 · see citing works
Mutation patterns in a population-based non-small cell lung cancer cohort and prognostic impact of concomitant mutations in KRAS and TP53 or STK11
Fleur, L. L., Falk-Sörqvist, E., Smeds, P., Berglund, A., Sundström, M., Mattsson, J. S., Brandén, E., Koyi, H., Isaksson, J., Brunnström, H., et al. (2019) · Lung Cancer · doi:10.1016/j.lungcan.2019.01.003 · Cited by 202 · see citing works
Once-daily savolitinib in Chinese patients with pulmonary sarcomatoid carcinomas and other non-small-cell lung cancers harbouring MET exon 14 skipping alterations: a multicentre, single-arm, open-label, phase 2 study
Lü, S., Fang, J., Li, X., Cao, L., Zhou, J., Guo, Q., Liang, Z., Cheng, Y., Jiang, L., Yang, N., et al. (2021) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(21)00084-9 · Cited by 207 · see citing works
The Impact of Smoking and TP53 Mutations in Lung Adenocarcinoma Patients with Targetable Mutations—The Lung Cancer Mutation Consortium (LCMC2)
Aisner, D. L., Sholl, L. M., Berry, L. D., Rossi, M. R., Chen, H., Fujimoto, J., Moreira, A. L., Ramalingam, S. S., Villaruz, L. C., Otterson, G. A., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-2289 · Cited by 206 · see citing works
Lung cancer in never smokers—the East Asian experience
Zhou, F., & Zhou, C. (2018) · Translational Lung Cancer Research · doi:10.21037/tlcr.2018.05.14 · Cited by 208 · see citing works
“com suggested that patients with METex14 skipping can derive clinical benefit from MET inhibitors (crizotinib and INC280) (97,101).”
Background
Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSé phase II trial
Moro‐Sibilot, D., Cozic, N., Pérol, M., Mazières, J., Otto, J., Souquet, P. J., Bahleda, R., Wislez, M., Zalcman, G., de Guibert, S., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz407 · Cited by 197 · see citing works
Crizotinib in MET -Deregulated or ROS1 -Rearranged Pretreated Non–Small Cell Lung Cancer (METROS): A Phase II, Prospective, Multicenter, Two-Arms Trial
Landi, L. M., Chiari, R., Tiseo, M., Federica D’Incà, Dazzi, C., Chella, A., Delmonte, A., Bonanno, L., Giannarelli, D., Cortinovis, D. L., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-0994 · Cited by 189 · see citing works
“METROS study also included patients with MET exon 14 mutations, accounting for less than 3% of the screened population, as expected according to literature data (7, 8).”
BackgroundInfluential
Novel therapeutic targets on the horizon for lung cancer
Tan, W.-L., Jain, A., Takano, A. M., Newell, E. W., Iyer, N. G., Lim, W., Tan, E.-H., Zhai, W., Hillmer, A. M., Tam, W. L., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30123-1 · Cited by 184 · see citing works
Sensitivity and Resistance of MET Exon 14 Mutations in Lung Cancer to Eight MET Tyrosine Kinase Inhibitors In Vitro
Fujino, T., Kobayashi, Y., Suda, K., Koga, T., Nishino, M., Ohara, S., Chiba, M., Shimoji, M., Tomizawa, K., Takemoto, T., et al. (2019) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2019.06.023 · Cited by 186 · see citing works
Noncoding RNAs regulate alternative splicing in Cancer
Liu, Y., Liu, X., Lin, C., Jia, X., Zhu, H., Song, J. H., & Zhang, Y. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01798-2 · Cited by 183 · see citing works
HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers
Moosavi, F., Giovannetti, E., Saso, L., & Firuzi, O. (2019) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408363.2019.1653821 · Cited by 177 · see citing works
“These mutations are very likely to confer sensitivity to MET targeted therapies [65,124,125].”
Background
Acquired Resistance to Crizotinib in NSCLC with MET Exon 14 Skipping
Heist, R. S., Sequist, L. V. D., Borger, D. R., Gainor, J. F., Arellano, R. S., Le, L. P., Dias-Santagata, D. C., Clark, J. W., Engelman, J. A., Shaw, A. T., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.06.013 · Cited by 173 · see citing works
The race to target MET exon 14 skipping alterations in non-small cell lung cancer: The Why, the How, the Who, the Unknown, and the Inevitable
Reungwetwattana, T., Liang, Y., Zhu, V. W., & Ou, S. I. (2016) · Lung Cancer · doi:10.1016/j.lungcan.2016.11.011 · Cited by 173 · see citing works
Self-citation
Capmatinib (INC280) Is Active Against Models of Non–Small Cell Lung Cancer and Other Cancer Types with Defined Mechanisms of MET Activation
Baltschukat, S., Engstler, B. S., Huang, A., Hao, H.-X., Tam, A., Wang, H. Q., Liang, J., DiMare, M. T., Bhang, H.-E. C., Wang, Y., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2814 · Cited by 163 · see citing works
Self-citation
MET in Lung Cancer: Biomarker Selection Based on Scientific Rationale
Salgia, R. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-16-0472 · Cited by 162 · see citing works
“In one patient with largecell carcinoma who was treated for over 5 months, there was a partial response comprising a 53% reduction in tumor, and in the other patient, who had squamous NSCLC that had failed prior therapies and was treated for 13 months, there was a partial response comprising a 61% reduction in tumor (…”
BackgroundSelf-citation
Management of advanced non-small cell lung cancers with known mutations or rearrangements: latest evidence and treatment approaches
Shea, M., Costa, D. B., & Rangachari, D. (2015) · Therapeutic Advances in Respiratory Disease · doi:10.1177/1753465815617871 · Cited by 157 · see citing works
“MET exon 14 skipping deletions can be found in 4% of lung ACs [Cancer Genome Atlas Research Network, 2014; Frampton et al. 2015].”
Background
Recent advances in the discovery of small molecule c-Met Kinase inhibitors
Parikh, P. K., & Ghate, M. D. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.08.044 · Cited by 157 · see citing works
DNA-Based versus RNA-Based Detection of MET Exon 14 Skipping Events in Lung Cancer
Davies, K. D., Lomboy, A., Lawrence, C. A., Yourshaw, M., Bocsi, G. T., Camidge, D. R., & Aisner, D. L. (2019) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2018.12.020 · Cited by 156 · see citing works
Emerging therapies for non-small cell lung cancer
Zhang, C., Leighl, N. B., Wu, Y.-L. L. C., & Zhong, W. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0731-8 · Cited by 153 · see citing works
MET alterations in NSCLC—Current Perspectives and Future Challenges
Remón, J., Hendriks, L. E. L., Mountzios, G., García‐Campelo, R., Saw, S. P. L., Uprety, D., Recondo, G., Villacampa, G. J., & Reck, M. (2022) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2022.10.015 · Cited by 150 · see citing works
Glesatinib Exhibits Antitumor Activity in Lung Cancer Models and Patients Harboring MET Exon 14 Mutations and Overcomes Mutation-mediated Resistance to Type I MET Inhibitors in Nonclinical Models
Engstrom, L. D., Aranda, R., Lee, M., Tovar, E. A., Essenburg, C. J., Madaj, Z., Chiang, H., Briere, D. M., Hallin, J. F., Lopez-Casas, P. P., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-1192 · Cited by 149 · see citing works
“MostMETex14 delmutations have been identified in lung adenocarcinoma, adenosquamous, or pulmonary sarcomatoid carcinoma subtypes, collectively comprise approximately 3% of non–small cell lung cancer (NSCLC), and are statistically exclusive with other known oncogenic drivers (4, 8, 9).”
Background
First-in-Human Phase I, Dose-Escalation and -Expansion Study of Telisotuzumab Vedotin, an Antibody–Drug Conjugate Targeting c-Met, in Patients With Advanced Solid Tumors
Strickler, J. H., Weekes, C. D., Nemunaitis, J. J., Ramanathan, R. K., Heist, R. S., Morgensztern, D., Angevin, E., Bauer, T. M., Yue, H., Motwani, M., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.78.7697 · Cited by 144 · see citing works
Self-citation
A 2015 update on predictive molecular pathology and its role in targeted cancer therapy: a review focussing on clinical relevance
Dietel, M., Jöhrens, K., von Laffert, M., Hummel, M., Bläker, H., Pfitzner, B. M., Lehmann, A., Denkert, C., Darb‐Esfahani, S., Lenze, D., et al. (2015) · Cancer Gene Therapy · doi:10.1038/cgt.2015.39 · Cited by 146 · see citing works
Oncogenic alterations in advanced NSCLC: a molecular super-highway
Friedlaender, A., Pérol, M., Banna, G. L., Parikh, K., & Addeo, A. (2024) · Biomarker Research · doi:10.1186/s40364-024-00566-0 · Cited by 144 · see citing works
“All potentially lead to constitutional MET receptor activation, with downstream proliferation signaling [208–210].”
Background
Clinicopathological implications of MET exon 14 mutations in non-small cell lung cancer – A systematic review and meta-analysis
Vuong, H. G., Ho, A. T. N., Altibi, A. M. A., Nakazawa, T., Katoh, R., & Kondo, T. (2018) · Lung Cancer · doi:10.1016/j.lungcan.2018.07.006 · Cited by 131 · see citing works
Targeted Therapy and Immunotherapy for Lung Cancer
Naylor, E. C., Desani, J., & Chung, P. K. (2016) · Surgical Oncology Clinics of North America · doi:10.1016/j.soc.2016.02.011 · Cited by 125 · see citing works
Targeted therapies for gastric cancer: failures and hopes from clinical trials
Apicella, M., Corso, S., & Giordano, S. (2017) · Oncotarget · doi:10.18632/oncotarget.14825 · Cited by 124 · see citing works
Exon 14 Deleted MET Receptor as a New Biomarker and Target in Cancers
Cortot, A. B., Kherrouche, Z., Descarpentries, C., Wislez, M., Baldacci, S., Furlan, A., & Tulasne, D. (2016) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djw262 · Cited by 124 · see citing works
“alterations across advanced cancers of various origins, including lung cancers and also gastric, colorectal, and brain cancers, although at a lower rate (41).”
Influential
The genomic landscape of Epstein-Barr virus-associated pulmonary lymphoepithelioma-like carcinoma
Hong, S., Liu, D., Luo, S., Fang, W., Zhan, J., Fu, S., Zhang, Y., Wu, X., Zhou, H., Chen, X., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10902-w · Cited by 124 · see citing works
Predictive biomarkers of anti-PD-1/PD-L1 therapy in NSCLC
Niu, M., Yi, M., Li, N., Luo, S., & Wu, K. (2021) · Experimental Hematology and Oncology · doi:10.1186/s40164-021-00211-8 · Cited by 125 · see citing works
“The mesenchymal epithelial transition (MET) exon 14 skipping alterations occur in 3%-4% of lung cancers [54].”
Background
Activation of KRAS Mediates Resistance to Targeted Therapy in MET Exon 14–mutant Non–small Cell Lung Cancer
Suzawa, K., Offin, M. D., Lu, D., Kurzatkowski, C., Vojnic, M., Smith, R. S., Sabari, J. K., Tai, H., Mattar, M. S., Khodos, I., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1640 · Cited by 123 · see citing works
“Responses to MET inhibitors, such as crizotinib and cabozantinib, have been reported in patients with lung cancer with METex14 alterations, including the PROFILE 1001 (NCT00585195) trial which found an objective response rate to crizotinib of 39% with a progression-free survival of 8 months in the 28 evaluable patient…”
Background
MET Oncogene in Non-Small Cell Lung Cancer: Mechanism of MET Dysregulation and Agents Targeting the HGF/c-Met Axis
Liang, H., & Wang, M. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s231257 · Cited by 123 · see citing works
Molecular pathology of lung cancer: current status and perspectives
Oberndorfer, F., & Müllauer, L. (2017) · Current Opinion in Oncology · doi:10.1097/cco.0000000000000429 · Cited by 119 · see citing works
Optimizing Mutation and Fusion Detection in NSCLC by Sequential DNA and RNA Sequencing
Cohen, D. B., Hondelink, L. M., Solleveld‐Westerink, N., Kolkman-Uljee, S. M., Ruano, D., Cleton-Jansen, A., von der Thüsen, J. H., Ramai, S. R. S., Postmus, P. E., van Roggen, J. F. G., et al. (2020) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2020.01.019 · Cited by 120 · see citing works
Targeted Therapy in Advanced and Metastatic Non-Small Cell Lung Cancer. An Update on Treatment of the Most Important Actionable Oncogenic Driver Alterations
König, D., Prince, S. S., & Rothschild, S. I. (2021) · Cancers · doi:10.3390/cancers13040804 · Cited by 114 · see citing works
“The other oncogenic alterations occur in less than 3% of patients with AC [49,50].”
Background
CompoundEGFRmutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma
Kim, E. Y., Cho, E. N., Park, H. S., Hong, J. Y., Lim, S., Youn, J. P., Hwang, S. Y., & Chang, Y. S. (2016) · Cancer Biology & Therapy · doi:10.1080/15384047.2016.1139235 · Cited by 116 · see citing works
“detected in the exon14 and exon skipping could not be detected by the applied technique.(26,27) Mutations in the MET kinase domain (c.”
Background
Bax/Bcl-2 Cascade Is Regulated by the EGFR Pathway: Therapeutic Targeting of Non-Small Cell Lung Cancer
Alam, M., Alam, S., Shamsi, A., Adnan, M., Elasbali, A. M., Al‐Soud, W. A., Alreshidi, M. M., Hawsawi, Y. M., Tippana, A., Pasupuleti, V. R., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.869672 · Cited by 118 · see citing works
Impact of MET inhibitors on survival among patients with non-small cell lung cancer harboring MET exon 14 mutations: a retrospective analysis
Awad, M. M., Leonardi, G. C., Kravets, S., Dahlberg, S. E., Drilon, A. E. D. C., Noonan, S. A., Camidge, D. R., Ou, S. I., Costa, D. B., Gadgeel, S. M., et al. (2019) · Lung Cancer · doi:10.1016/j.lungcan.2019.05.011 · Cited by 111 · see citing works
Self-citation
Comprehensive Characterization of Oncogenic Drivers in Asian Lung Adenocarcinoma
Li, S., Choi, Y., Gong, Z., Liu, X., Lira, M. E., Kan, Z., Oh, E., Wang, J., Ting, J. C., Ye, X. S., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.08.142 · Cited by 110 · see citing works
“A cell line (NCIH596) that expres ses MET∆Ex14 was sensitive to MET inhibition in vitro and in vivo (40), and data from a few recent reports demonstrated the clinical efficacy of crizotinib an d cabozantinib in MET ∆Ex14 LUAD patients (41, 42).”
Background
MET Exon 14 Skipping in Non-Small Cell Lung Cancer
Heist, R. S., Shim, H. S., Gingipally, S., Mino-Kenudson, M. A., Le, L. P., Gainor, J. F., Zheng, Z., Aryee, M. J., Xia, J., Jia, P., et al. (2016) · The Oncologist · doi:10.1634/theoncologist.2015-0510 · Cited by 107 · see citing works
Co-occurring Alterations in the RAS–MAPK Pathway Limit Response to MET Inhibitor Treatment in MET Exon 14 Skipping Mutation-Positive Lung Cancer
Rotow, J. K., Gui, P., Wu, W., Raymond, V. M., Lanman, R. B., Kaye, F. J., Peled, N., de la Cruz, F. F., Nadres, B., Corcoran, R. B., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1667 · Cited by 109 · see citing works
“Somatic MET mutations leading to splicing-mediated loss of exon 14 and subsequent MET overexpression are an emerging therapeutic target present in 2% to 4% of lung adenocarcinomas (1, 2).”
Self-citation
Tepotinib Efficacy and Safety in Patients with MET Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice
Le, X., Sakai, H., Felip, E., Veillon, R., Garassino, M. C., Raskin, J., Cortot, A. B., Viteri, S., Mazières, J., Smit, E. F., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-2733 · Cited by 106 · see citing works
MET-Driven Resistance to Dual EGFR and BRAF Blockade May Be Overcome by Switching from EGFR to MET Inhibition in BRAF -Mutated Colorectal Cancer
Pietrantonio, F., Oddo, D., Gloghini, A., Valtorta, E., Berenato, R., Barault, L., Caporale, M., Busico, A., Morano, F., Gualeni, A. V., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0297 · Cited by 103 · see citing works
“in lung cancer (12), we assessed MDM2 gene copy number by ISH.”
Method
Intracranial Activity of Cabozantinib in MET Exon 14–Positive NSCLC with Brain Metastases
Klempner, S. J., Borghei, A., Hakimian, B., Ali, S. M., & Ou, S. I. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.09.127 · Cited by 103 · see citing works
“Although systemic response to MET TKIs is well documented, the intracranial activity was not reported in a capmatinibsensitive patient with known brain metastases.(1) Ongoing trials of type I MET TKIs, including capmatinib (NCT02750215), tepotinib (NCT02864992), and crizotinib (NCT00585195), will add to our understand…”
BackgroundInfluentialSelf-citation
METExon 14 Skipping Mutations in Non–Small-Cell Lung Cancer: An Overview of Biology, Clinical Outcomes, and Testing Considerations
Socinski, M. A., Pennell, N. A., & Davies, K. D. (2021) · JCO Precision Oncology · doi:10.1200/po.20.00516 · Cited by 104 · see citing works
“Among them, both MSK-IMPACT and FoundationOne CDx (Foundation Medicine Inc, Cambridge, MA) reliably detect a wide array of alterations leading to MET exon 14 skipping, without the need for supplemental RNA-based testing.(3,20,67,72)”
BackgroundMethodInfluential
Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism-Driven Clinical Trials
Suh, J. H., Johnson, A., Albacker, L. A., Wang, K., Chmielecki, J., Frampton, G. M., Gay, L. M., Elvin, J. A., Vergilio, J., Ali, S. M., et al. (2016) · The Oncologist · doi:10.1634/theoncologist.2016-0030 · Cited by 102 · see citing works
Self-citation
Next Generation Sequencing Technology in Lung Cancer Diagnosis
Cainap, C. I., Bălăcescu, O., Cainap, S. S., & Pop, L. (2021) · Biology · doi:10.3390/biology10090864 · Cited by 104 · see citing works
“In addition, NGS has successfully been used to identify lung cancer patients that had MET exon14 skipping alterations [55].”
Method
MET -Oncogenic and JAK2 -Inactivating Alterations Are Independent Factors That Affect Regulation of PD-L1 Expression in Lung Cancer
Saigí, M., Alburquerque-Béjar, J. J., Leer, A. M., Pereira, C. A., Pros, E., Romero, O. A., Baixeras, N., Esteve‐Codina, A., Nadal, E., Brambilla, E. M., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0267 · Cited by 102 · see citing works
“METex14mutations are known to increase MET protein stability, which have oncogenic potential and confer sensitivity to crizotinib, a MET-tyrosine kinase inhibitor (24, 25).”
Background
Molecular correlates of response to capmatinib in advanced non-small-cell lung cancer: clinical and biomarker results from a phase I trial
Schüler, M., Berardi, R., Lim, W., de Jonge, M. J. A., Bauer, T. M., Azaro, A., Gottfried, M., Han, J., Lee, D. H., Wollner, M., et al. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.03.293 · Cited by 97 · see citing works
“Nausea 28 (60) 2 (4) Peripheral edema 25 (46) 2 (4) Vomiting 22 (40) 2 (4) Decreased appetite 17 (31) 2 (4) Fatigue 15 (27) 2 (4) Dyspnea 14 (26) 2 (4) Blood creatinine increased 13 (24) 0 Asthenia 11 (20) 2 (4) Diarrhea 11 (20) 2 (4) Back pain 10 (18) 1 (2) Hypoalbuminemia 9 (16) 3 (6) Alanine aminotransferase increa…”
Self-citation
Personalized Medicine in the Oncology Clinic: Implementation and Outcomes of the Johns Hopkins Molecular Tumor Board
Dalton, W. B., Forde, P. M., Kang, H., Connolly, R. M., Stearns, V., Gocke, C. D., Eshleman, J. R., Axilbund, J. E., Petry, D., Geoghegan, C., et al. (2017) · JCO Precision Oncology · doi:10.1200/po.16.00046 · Cited by 94 · see citing works
MET Expression in Advanced Non–Small-Cell Lung Cancer: Effect on Clinical Outcomes of Chemotherapy, Targeted Therapy, and Immunotherapy
Reis, H., Metzenmacher, M., Goetz, M., Savvidou, N., Darwiche, K., Aigner, C., Herold, T., Eberhardt, W., Skiba, C., Hense, J., et al. (2018) · Clinical Lung Cancer · doi:10.1016/j.cllc.2018.03.010 · Cited by 94 · see citing works
Circular RNAs and RNA Splice Variants as Biomarkers for Prognosis and Therapeutic Response in the Liquid Biopsies of Lung Cancer Patients
de Fraipont, F., Gazzéri, S., Cho, W. C. S., & Eymin, B. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00390 · Cited by 93 · see citing works
STMN1 upregulation mediates hepatocellular carcinoma and hepatic stellate cell crosstalk to aggravate cancer by triggering the MET pathway
Zhang, R., Gao, X., Zuo, J., Hu, B., Yang, J., Zhao, J., & Chen, J. (2019) · Cancer Science · doi:10.1111/cas.14262 · Cited by 94 · see citing works

Abstract 1118: Activation of MET via diverse exon 14 skipping mutations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors
Frampton, G. M., Ali, S. M., Chmielecki, J., Rosenzweig, M. R., Brennan, T. A., Chalmers, Z. R., Elvin, J. A., Fichtenholtz, A., Gowan, K., Greenbowe, J. R., et al. (2015) · Cancer Research · doi:10.1158/1538-7445.am2015-1118 · Cited by 10 · see citing works
Self-citation
Comprehensive genomic profiling (CGP) of advanced cancers to identify MET exon 14 alterations that confer sensitivity to MET inhibitors.
Frampton, G. M., Ali, S. M., Rosenzweig, M. R., Goldman, J. W., Lee, C. B., Weiss, J., Bufill, J. A., Salgia, R., Jahanzeb, M., Konduri, K., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.33.15_suppl.11007 · Cited by 5 · see citing works
Self-citation
Characterization of MET exon 14 skipping in pancancer.
Li, F., Chen, J., Zhang, X., Yang, D., Xia, L., Wang, D., Jin, K., Zhu, J., Fang, Y., Wang, C., et al. (2022) · Journal of Clinical Oncology · doi:10.1200/jco.2022.40.16_suppl.e20530
Comprehensive genomic profiling of 298 lung cancers of varying histologies harboring MET exon 14 alterations.
Ou, S. I., Frampton, G. M., Suh, J. H., Chalmers, Z. R., Rosenweig, M., Goldman, J. W., Forde, P. M., Leuenberger, K., Peled, N., Kalemkerian, G. P., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.9021 · Cited by 1 · see citing works
Self-citation
MET exon 14 mutations in advanced lung adenocarcinoma: Frequency and coexisting alterations.
Bruno, R., Lupi, C., Landi, L. M., Alì, G., Sensi, E., Proietti, A., Giannini, R., Condello, V., Denaro, M., Giordano, M., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.35.15_suppl.e20656 · Cited by 3 · see citing works

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
Publisher: American Association for Cancer Research (AACR)
Published: 2015-08-01
Volume: 5
Issue: 8
Pages: 850-859
ISSN: 2159-8274 (ISSN-L)
2159-8290
DOI: 10.1158/2159-8290.cd-15-0285
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 · 2014: 1 · 2013: 1
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
Health Sciences › Medicine › Pathology and Forensic Medicine › 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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Activation of MET via Diverse Exon 14 Splicing Alterations Occurs in Multiple Tumor Types and Confers Clinical Sensitivity to MET Inhibitors

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