The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib
Open accessAbstract
In human lung adenocarcinomas harboring EGFR mutations, a second-site point mutation that substitutes methionine for threonine at position 790 (T790M) is associated with approximately half of cases of acquired resistance to the EGFR kinase inhibitors, gefitinib and erlotinib. To identify other potential mechanisms that contribute to disease progression, we used array-based comparative genomic hybridization (aCGH) to compare genomic profiles of EGFR mutant tumors from untreated patients with those from patients with acquired resistance. Among three loci demonstrating recurrent copy number alterations (CNAs) specific to the acquired resistance set, one contained the MET proto-oncogene. Collectively, analysis of tumor samples from multiple independent patient cohorts revealed that MET was amplified in tumors from 9 of 43 (21%) patients with acquired resistance but in only two tumors from 62 untreated patients (3%) (P = 0.007, Fisher's Exact test). Among 10 resistant tumors from the nine patients with MET amplification, 4 also harbored the EGFR(T790M) mutation. We also found that an existing EGFR mutant lung adenocarcinoma cell line, NCI-H820, harbors MET amplification in addition to a drug-sensitive EGFR mutation and the T790M change. Growth inhibition studies demonstrate that these cells are resistant to both erlotinib and an irreversible EGFR inhibitor (CL-387,785) but sensitive to a multikinase inhibitor (XL880) with potent activity against MET. Taken together, these data suggest that MET amplification occurs independently of EGFR(T790M) mutations and that MET may be a clinically relevant therapeutic target for some patients with acquired resistance to gefitinib or erlotinib.
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“Amplification of the MET gene was found in EGFR mutant cancers with acquired resistance to EGFR TKIs but not in pre-treatment biopsies (Bean et al., 2007; Engelman et al., 2007).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Bean et al., 2007
In the citing paper
“the (acquired) alterations identified in a single biopsy may not reflect all of the resistant clones in multiple metastatic sites in an individual patient (Bean et al., 2007; Engelman et al., 2007; Turke et al., 2010).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Bean et al., 2007
Citations
Cites
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EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368
MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
Engelman, J. A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J. O., Lindeman, N., Gale, C.-M., Zhao, X., Christensen, J., et al. (2007) · Science · doi:10.1126/science.1141478 · Cited by 4,496
Pao, W., Miller, V., Zakowski, M., Doherty, J., Politi, K., Sarkaria, I., Singh, B., Heelan, R., Rusch, V., Fulton, L., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405220101 · Cited by 4,338
Self-citationEGFR Mutation and Resistance of Non–Small-Cell Lung Cancer to Gefitinib
Kobayashi, S., Boggon, T. J., Dayaram, T., Jänne, P. A., Kocher, O., Meyerson, M., Johnson, B. E., Eck, M. J., Tenen, D. G., & Halmos, B. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa044238 · Cited by 3,964
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Self-citationMet, metastasis, motility and more
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Circular binary segmentation for the analysis of array-based DNA copy number data
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Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib
Kwak, E. L., Sordella, R., Bell, D. W., Godin-Heymann, N., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Driscoll, D. R., Fidias, P. M., Lynch, T. J., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502860102 · Cited by 966
Research works printed but not linked: 1
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Cited by
Sorted by citations
Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors
Sequist, L. V., Waltman, B. A., Dias-Santagata, D., Digumarthy, S., Turke, A. B., Fidias, P., Bergethon, K., Shaw, A. T., Gettinger, S., Cosper, A. K., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002003 · Cited by 3,499
Influence of tumour micro-environment heterogeneity on therapeutic response
Junttila, M. R., & de Sauvage, F. J. (2013) · Nature · doi:10.1038/nature12626 · Cited by 2,694
Metastasis: from dissemination to organ-specific colonization
Nguyen, D. X., Bos, P. D., & Massagué, J. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2622 · Cited by 2,716
Yu, H. A., Arcila, M. E., Rekhtman, N., Sima, C. S., Zakowski, M. F., Pao, W., Kris, M. G., Miller, V. A., Ladanyi, M., & Riely, G. J. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2246 · Cited by 2,454
Self-citationHerbst, R. S., Heymach, J. V., & Lippman, S. M. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0802714 · Cited by 2,435
Metadata
- Authors
- Bean, J., Brennan, C., Shih, J.-Y., Riely, G., Viale, A., Wang, L., Chitale, D., Motoi, N., Szoke, J., Broderick, S., Balak, M., Chang, W.-C., Yu, C.-J., Gazdar, A., Pass, H., Rusch, V., Gerald, W., Huang, S.-F., Yang, P.-C., Miller, V., Ladanyi, M., Yang, C.-H., & Pao, W.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- National Taiwan University (TW)
- Department of Pathology, Memorial Sloan–Kettering Cancer Center, New York, NY 10021;
- Chang Gung Memorial Hospital (TW)
- The University of Texas Southwestern Medical Center (US)
- NYU Langone Health (US)
- National Health Research Institutes (TW)
- National Taiwan University Hospital (TW)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-12-26
- Volume
- 104
- Issue
- 52
- Pages
- 20932-20937
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2409244
- OpenAlex
- W2093613683
- Cited by
- 1,598
- References
- 37
- Citations by year
- 2026: 17 · 2025: 19 · 2024: 33 · 2023: 42 · 2022: 59 · 2021: 54 · 2020: 78 · 2019: 78 · 2018: 100 · 2017: 89 · 2016: 116 · 2015: 135 · 2014: 124 · 2013: 148 · 2012: 126
- FWCI
- 71.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Conquer Cancer Foundation
- Memorial Sloan-Kettering Cancer Center
- Exelixis
- National Cancer Institute (U01 CA 84999, P50CA75907, R01CA121210, U01CA084999, K08CA097980, R21CA115051)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- MET amplification, T790M mutation, EGFR mutation, lung adenocarcinoma, acquired drug resistance, gefitinib, erlotinib, EGFR tyrosine kinase inhibitors, copy number alterations, multikinase inhibitor, therapeutic target
- MeSH terms
- Erlotinib Hydrochloride, Gefitinib, Proto-Oncogene Mas, Adenocarcinoma, Antineoplastic Agents, Chromosomes, Human, Pair 7, DNA Mutational Analysis, Humans, Lung Neoplasms, Mutation, Quinazolines, Cohort Studies, Gene Expression Regulation, Neoplastic, In Situ Hybridization, Fluorescence, Drug Resistance, Neoplasm, Proto-Oncogene Proteins c-met, Protein Kinase Inhibitors, ErbB Receptors
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