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Cited by 1,598Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchCancer Genomics and Diagnostics

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 access
Bean, James, Brennan, Cameron, Shih, Jin-Yuan, Riely, Gregory, Viale, Agnes, Wang, Lu, Chitale, Dhananjay, Motoi, Noriko, Szoke, Janos, Broderick, Stephen, Balak, Marissa, Chang, Wen-Cheng, Yu, Chong-Jen, Gazdar, Adi, Pass, Harvey, Rusch, Valerie, Gerald, William, Huang, Shiu-Feng, Yang, Pan-Chyr, Miller, Vincent, Ladanyi, Marc, Yang, Chih-Hsin, Pao, William·2007·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0710370104PMC PMC2409244
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Abstract

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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Crossref · 10.1073/pnas.0710370104

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  1. BA Weir, MS Woo, G Getz, S Perner, L. Ding, R Beroukhim, WM Lin, MA Province, A Kraja, L Johnson, et al. Nature, 10.1038. (2007).

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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
DOI
10.1073/pnas.0710370104
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
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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