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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“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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“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…”
BackgroundKohsaka, 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
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
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
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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
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 217
“com suggested that patients with METex14 skipping can derive clinical benefit from MET inhibitors (crizotinib and INC280) (97,101).”
BackgroundCrizotinib 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 202
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 193
“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).”
BackgroundInfluentialNovel 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 185
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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 187
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 178
“These mutations are very likely to confer sensitivity to MET targeted therapies [65,124,125].”
BackgroundAcquired 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
Reungwetwattana, T., Liang, Y., Zhu, V. W., & Ou, S. I. (2016) · Lung Cancer · doi:10.1016/j.lungcan.2016.11.011 · Cited by 177
Self-citationBaltschukat, 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 167
Self-citationMET 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
“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-citationShea, M., Costa, D. B., & Rangachari, D. (2015) · Therapeutic Advances in Respiratory Disease · doi:10.1177/1753465815617871 · Cited by 158
“MET exon 14 skipping deletions can be found in 4% of lung ACs [Cancer Genome Atlas Research Network, 2014; Frampton et al. 2015].”
BackgroundRecent 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
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
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 159
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 156
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
“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).”
BackgroundStrickler, 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
Self-citationDietel, 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 150
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 150
“All potentially lead to constitutional MET receptor activation, with downstream proliferation signaling [208–210].”
BackgroundVuong, 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
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 129
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 126
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
“alterations across advanced cancers of various origins, including lung cancers and also gastric, colorectal, and brain cancers, although at a lower rate (41).”
InfluentialThe 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
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 129
“The mesenchymal epithelial transition (MET) exon 14 skipping alterations occur in 3%-4% of lung cancers [54].”
BackgroundSuzawa, 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 129
“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…”
BackgroundLiang, H., & Wang, M. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s231257 · Cited by 123
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 122
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 123
König, D., Prince, S. S., & Rothschild, S. I. (2021) · Cancers · doi:10.3390/cancers13040804 · Cited by 119
“The other oncogenic alterations occur in less than 3% of patients with AC [49,50].”
BackgroundKim, 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 117
“detected in the exon14 and exon skipping could not be detected by the applied technique.(26,27) Mutations in the MET kinase domain (c.”
BackgroundAlam, 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 122
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 112
Self-citationComprehensive 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 114
“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).”
BackgroundMET 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 111
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
“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-citationLe, 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
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
“in lung cancer (12), we assessed MDM2 gene copy number by ISH.”
MethodIntracranial 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
“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-citationSocinski, M. A., Pennell, N. A., & Davies, K. D. (2021) · JCO Precision Oncology · doi:10.1200/po.20.00516 · Cited by 104
“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)”
BackgroundMethodInfluentialSuh, 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 104
Self-citationNext 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 109
“In addition, NGS has successfully been used to identify lung cancer patients that had MET exon14 skipping alterations [55].”
MethodSaigí, 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 104
“METex14mutations are known to increase MET protein stability, which have oncogenic potential and confer sensitivity to crizotinib, a MET-tyrosine kinase inhibitor (24, 25).”
BackgroundSchüler, 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
“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-citationDalton, 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 97
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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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