Intragenic ERBB2 kinase mutations in tumours

Stephens, Philip; Hunter, Chris; Bignell, Graham; Edkins, Sarah; Davies, Helen; Teague, Jon; Stevens, Claire; O'Meara, Sarah; Smith, Raffaella; Parker, Adrian; Barthorpe, Andy; Blow, Matthew; Brackenbury, Lisa; Butler, Adam; Clarke, Oliver; Cole, Jennifer; Dicks, Ed; Dike, Angus; Drozd, Anja; Edwards, Ken; Forbes, Simon; Foster, Rebecca; Gray, Kristian; Greenman, Chris; Halliday, Kelly; Hills, Katy; Kosmidou, Vivienne; Lugg, Richard; Menzies, Andy; Perry, Janet; Petty, Robert; Raine, Keiran; Ratford, Lewis; Shepherd, Rebecca; Small, Alexandra; Stephens, Yvonne; Tofts, Calli; Varian, Jennifer; West, Sofie; Widaa, Sara; Yates, Andrew; Brasseur, Francis; Cooper, Colin S.; Flanagan, Adrienne M.; Knowles, Margaret; Leung, Suet Y.; Louis, David N.; Looijenga, Leendert H. J.; Malkowicz, Bruce; Pierotti, Marco A.

doi:10.1038/431525b

Cited by 802Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchCancer Genomics and Diagnostics

Intragenic ERBB2 kinase mutations in tumours

Stephens, Philip, Hunter, Chris, Bignell, Graham, Edkins, Sarah, Davies, Helen, Teague, Jon, Stevens, Claire, O'Meara, Sarah +52 more·2004·Nature

DOI 10.1038/431525b

Open this paper in CoChat — free account

Abstract

The protein-kinase family is the most frequently mutated gene family found in human cancer and faulty kinase enzymes are being investigated as promising targets for the design of antitumour therapies. We have sequenced the gene encoding the transmembrane protein tyrosine kinase ERBB2 (also known as HER2 or Neu) from 120 primary lung tumours and identified 4% that have mutations within the kinase domain; in the adenocarcinoma subtype of lung cancer, 10% of cases had mutations. ERBB2 inhibitors, which have so far proved to be ineffective in treating lung cancer, should now be clinically re-evaluated in the specific subset of patients with lung cancer whose tumours carry ERBB2 mutations.

Integrity signals

Registry

Crossref · 10.1038/431525b

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

The A775_G776insYVMA mutation accounts for most HER2 exon 20 mutations observed in NSCLC.
“with the A775_G776insYVMA mutation accounting for most of the mutations seen in NSCLC (17–21).”
From Response Heterogeneity of EGFR and HER2 Exon 20 Insertions to Covalent EGFR and HER2 Inhibitors (2017) · cites this paper as [17]
HER2 mutations have been found in a small proportion of lung, gastric, colorectal, breast and head and neck cancers.
“HER2 mutations have been found in a small proportion of lung, gastric, colorectal, breast and head and neck cancers (Lee et al., 2006; Ross et al., 2013; Stephens et al., 2004; Willmore-Payne et al., 2006).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Stephens et al., 2004

Human Breast Cancer: Correlation of Relapse and Survival with Amplification of the HER-2/ neu Oncogene
Slamon, D. J., Clark, G. M., Wong, S. G., Levin, W. J., Ullrich, A., & McGuire, W. L. (1987) · Science · doi:10.1126/science.3798106 · Cited by 11,760 · see citing works
Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to Gefitinib
Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Haserlat, S. M., Supko, J. G., Haluska, F. G., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040938 · Cited by 11,486 · see citing works
Self-citation
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 · see citing works
A census of human cancer genes
Futreal, P. A., Coin, L., Marshall, M., Down, T., Hubbard, T., Wooster, R., Rahman, N., & Stratton, M. R. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1299 · Cited by 3,184 · see citing works
Self-citation
Opportunities and challenges in the development of kinase inhibitor therapy for cancerPreprint
Sawyers, C. L. (2003) · Genes & Development · doi:10.1101/gad.1152403 · Cited by 170 · see citing works
The role of HER2/neu expression and trastuzumab in non-small cell lung cancer
Hirsch, F. R., & Langer, C. J. (2004) · Seminars in Oncology · doi:10.1053/j.seminoncol.2003.12.018 · Cited by 64 · see citing works
Toward Customized Trastuzumab in HER-2/neu-Overexpressing Non-Small-Cell Lung Cancers
Rosell, R. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.01.904 · Cited by 30 · see citing works

Flagged first, then by citations

Sorted by citations

Comprehensive genomic characterization defines human glioblastoma genes and core pathways
The Cancer Genome Atlas Research Network (2008) · Nature · doi:10.1038/nature07385 · Cited by 7,735 · see citing works
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
The cancer genome
Stratton, M. R., Campbell, P. J., & Futreal, P. A. (2009) · Nature · doi:10.1038/nature07943 · Cited by 3,459 · see citing works
ERBB receptors and cancer: the complexity of targeted inhibitors
Hynes, N. E., & Lane, H. A. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1609 · Cited by 3,313 · see citing works
“Intriguingly, mutations in the kinase domain of ERBB2 have been identified in a small number of NSCLC”
Background
Epidermal growth factor receptor mutations in lung cancer
Sharma, S. V., Bell, D. W., Settleman, J., & Haber, D. A. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2088 · Cited by 3,170 · see citing works
Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer
Roberts, P. J., & Der, C. J. (2007) · Oncogene · doi:10.1038/sj.onc.1210422 · Cited by 2,788 · see citing works
“, EGFR and HER2) can cause hyperactivation of Ras leading to upregulated MAPK signaling (Lynch et al., 2004; Stephens et al., 2004; Hynes and Lane, 2005).”
Background
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
Global Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung Cancer
Rikova, K., Guo, A., Zeng, Q., Possemato, A., Yu, J., Haack, H., Nardone, J., Lee, K., Reeves, C., Li, Y., et al. (2007) · Cell · doi:10.1016/j.cell.2007.11.025 · Cited by 2,317 · see citing works
An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage
Newman, A. M., Bratman, S. V., To, J., Wynne, J. F., Eclov, N. C. W., Modlin, L. A., Liu, C. L., Neal, J. W., Wakelee, H. A., Merritt, R. E., et al. (2014) · Nature Medicine · doi:10.1038/nm.3519 · Cited by 2,220 · see citing works
Exploiting the PI3K/AKT Pathway for Cancer Drug Discovery
Hennessy, B. T., Smith, D. L., Ram, P. T., Lu, Y., & Mills, G. B. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1902 · Cited by 2,183 · see citing works
Epidermal growth factor receptor (EGFR) signaling in cancer
Normanno, N., Luca, A. D., Bianco, C., Strizzi, L., Mancino, M., Maiello, M. R., Carotenuto, A., Feo, G. D., Caponigro, F., & Salomon, D. S. (2005) · Gene · doi:10.1016/j.gene.2005.10.018 · Cited by 2,035 · see citing works
Non-small-cell lung cancers: a heterogeneous set of diseases
Chen, Z., Brainson, C. F., Hammerman, P. S., Kim, C. F., & Wong, K. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3775 · Cited by 1,936 · see citing works
Erlotinib in Lung Cancer — Molecular and Clinical Predictors of Outcome
Tsao, M., Sakurada, A., Cutz, J.-C., Zhu, C., Kamel‐Reid, S., Squire, J. A., Lorimer, I. A. J., Zhang, T., Liu, G., Daneshmand, M., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050736 · Cited by 1,815 · see citing works
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
PI3K pathway alterations in cancer: variations on a theme
Yuan, T. L., & Cantley, L. C. (2008) · Oncogene · doi:10.1038/onc.2008.245 · Cited by 1,845 · see citing works
KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib
Pao, W. J., Wang, T. Y., Riely, G. J., Miller, V. A., Pan, Q., Ladanyi, M., Zakowski, M. F., Heelan, R. T., Kris, M. G., & VARMUS, H. E. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020017 · Cited by 1,517 · see citing works
BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models
Li, D., Ambrogio, L., Shimamura, T., Kubo, S., Takahashi, M., Chirieac, L. R., Padera, R. F., Shapiro, G. I., Baum, A., Himmelsbach, F., et al. (2008) · Oncogene · doi:10.1038/onc.2008.109 · Cited by 1,447 · see citing works
Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors
Mellinghoff, I. K., Wang, M. Y., Vivanco, I., Haas-Kogan, D. A., Zhu, S., Dia, E. Q., Lu, K. V., Yoshimoto, K., Huang, J. H. Y., Chute, D. J., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051918 · Cited by 1,442 · see citing works
Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications
Iqbal, N., & Iqbal, N. (2014) · Molecular Biology International · doi:10.1155/2014/852748 · Cited by 1,409 · see citing works
Tyrosine Kinases as Targets for Cancer Therapy
Krause, D. S., & Etten, R. A. V. (2005) · New England Journal of Medicine · doi:10.1056/nejmra044389 · Cited by 1,376 · see citing works
The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis
Moasser, M. M. (2007) · Oncogene · doi:10.1038/sj.onc.1210477 · Cited by 1,229 · see citing works
“Somatic mutations within the HER2 kinase domain have been described in a small subset of lung cancers, predominantly in Asian populations, and very rarely in gastric, colorectal and breast cancers (Figure 1, region D) (Stephens et al., 2004; Shigematsu et al., 2005; Lee et al., 2006).”
Background
Autophagy in malignant transformation and cancer progression
Galluzzi, L., Pietrocola, F., Bravo‐San Pedro, J. M., Amaravadi, R. K., Baehrecke, E. H., Cecconi, F., Codogno, P., Debnath, J., Gewirtz, D. A., Karantza, V., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490784 · Cited by 1,182 · see citing works
“…class I phosphatidyl-inositol 3-kinases (PI3Ks) and phosphoinositide-dependent protein kinase 1 (PDPK1) (Slamon et al , 1987; Irby et al , 1999; Shayesteh et al , 1999; Ma et al , 2000; Paez et al , 2004; Stephens et al , 2004; Carpten et al , 2007; Sen & Johnson, 2011; Chinen et al , 2014).”
Sequence analysis of mutations and translocations across breast cancer subtypes
Banerji, S. O., Cibulskis, K., Rangel‐Escareño, C., Brown, K., Carter, S. L., Frederick, A. M., Lawrence, M. S., Sivachenko, A., Sougnez, C. L., Zou, L., et al. (2012) · Nature · doi:10.1038/nature11154 · Cited by 1,181 · see citing works
New driver mutations in non-small-cell lung cancer
Pao, W. J., & Girard, N. (2011) · The Lancet Oncology · doi:10.1016/s1470-2045(10)70087-5 · Cited by 1,172 · see citing works
Targeted cancer therapy
Sawyers, C. L. (2004) · Nature · doi:10.1038/nature03095 · Cited by 1,171 · see citing works
Advances in understanding cancer genomes through second-generation sequencing
Meyerson, M. M., Gabriel, S., & Getz, G. A. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2841 · Cited by 1,114 · see citing works
Characterizing the cancer genome in lung adenocarcinoma
Weir, B. A., Woo, M. S., Getz, G., Perner, S., Ding, L., Beroukhim, R., Lin, W. M., Province, M. A., Kraja, A., Johnson, L. A., et al. (2007) · Nature · doi:10.1038/nature06358 · Cited by 1,105 · 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
ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics
Arteaga, C. L., & Engelman, J. A. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.02.025 · Cited by 1,048 · see citing works
“HER2mutations have been found in a small proportion of lung, gastric, colorectal, breast, and head and neck cancers (Lee et al., 2006; Ross et al., 2013; Stephens et al., 2004; WillmorePayne et al., 2006).”
Background
Trastuzumab Deruxtecan in HER2 -Mutant Non–Small-Cell Lung Cancer
Li, B. T., Smit, E. F., Goto, Y., Nakagawa, K., Udagawa, H., Mazières, J., Nagasaka, M., Bazhenova, L. A., Saltos, A. N., Felip, E., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2112431 · Cited by 1,046 · see citing works
Diverse somatic mutation patterns and pathway alterations in human cancers
Kan, Z., Jaiswal, B. S., Stinson, J., Janakiraman, V., Bhatt, D., Stern, H. M., Yue, P., Haverty, P. M., Bourgon, R., Zheng, J., et al. (2010) · Nature · doi:10.1038/nature09208 · Cited by 1,018 · see citing works
The ERBB network: at last, cancer therapy meets systems biology
Yarden, Y., & Pines, G. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3309 · Cited by 998 · see citing works
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
The Epidermal Growth Factor Receptor Pathway: A Model for Targeted Therapy
Scaltriti, M., & Baselga, J. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1554 · Cited by 913 · see citing works
Mechanisms of Disease: understanding resistance to HER2-targeted therapy in human breast cancer
Nahta, R., Yu, D., Hung, M., Hortobágyi, G. N., & Esteva, F. J. (2006) · Nature Clinical Practice Oncology · doi:10.1038/ncponc0509 · Cited by 916 · see citing works
Activating HER2 Mutations in HER2 Gene Amplification Negative Breast Cancer
Bose, R., Kavuri, S. M., Searleman, A. C., Shen, W., Shen, D., Koboldt, D. C., Monsey, J. D., Goel, N. J., Aronson, A. B., Li, S., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0349 · Cited by 869 · see citing works
New driver mutations in non-small-cell lung cancer
Tanoue, L. T. (2012) · Yearbook of Pulmonary Disease · doi:10.1016/j.ypdi.2012.01.036 · Cited by 833 · see citing works
Activating mutations in ALK provide a therapeutic target in neuroblastoma
George, R. E., Sanda, T., Hanna, M., Fröhling, S., II, W. L., Zhang, J., Ahn, Y., Zhou, W., London, W. B., McGrady, P., et al. (2008) · Nature · doi:10.1038/nature07397 · Cited by 893 · see citing works
Non–Small Cell Lung Cancer
_, _. (2008) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2008.0021 · Cited by 737 · see citing works
PF00299804, an Irreversible Pan-ERBB Inhibitor, Is Effective in Lung Cancer Models with EGFR and ERBB2 Mutations that Are Resistant to Gefitinib
Engelman, J. A., Zejnullahu, K., Gale, C.-M., Lifshits, E., Gonzales, A. J., Shimamura, T., Zhao, F., Vincent, P. W., Naumov, G. N., Bradner, J. E., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1885 · Cited by 730 · see citing works
Critical Update and Emerging Trends in Epidermal Growth Factor Receptor Targeting in Cancer
Baselga, J. M., & Arteaga, C. L. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.11.890 · Cited by 721 · see citing works
Epidermal Growth Factor Receptor Targeting in Cancer
Mendelsohn, J. M., & Baselga, J. M. (2006) · Seminars in Oncology · doi:10.1053/j.seminoncol.2006.04.003 · Cited by 693 · see citing works
Epidermal Growth Factor Receptor Gene Mutations and Increased Copy Numbers Predict Gefitinib Sensitivity in Patients With Recurrent Non–Small-Cell Lung Cancer
Takano, T., Ohe, Y., Sakamoto, H., Tsuta, K., Matsuno, Y., Tateishi, U., Yamamoto, S., Nokihara, H., Yamamoto, N., Sekine, I., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.01.0793 · Cited by 691 · see citing works
Exploring the Genomes of Cancer Cells: Progress and Promise
Stratton, M. R. (2011) · Science · doi:10.1126/science.1204040 · Cited by 688 · see citing works
Somatic Mutations of the HER2 Kinase Domain in Lung Adenocarcinomas
Shigematsu, H., Takahashi, T., Nomura, M., Majmudar, K., Suzuki, M., Lee, H., Wistuba, I. I., Fong, K. M., Toyooka, S., Shimizu, N., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4235 · Cited by 678 · see citing works
“Recently, mutations of HER2 were reported in lung adenocarcinomas and offer the potential of additional therapy targeted at the altered protein (22).”
BackgroundResultInfluential
Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies
Jordan, E. J., Kim, H. R., Arcila, M. E., Barron, D., Chakravarty, D., Gao, J., Chang, M. T., Ni, A., Kundra, R., Jonsson, P., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1337 · Cited by 643 · see citing works
Lung Cancer That Harbors an HER2 Mutation: Epidemiologic Characteristics and Therapeutic Perspectives
Mazières, J., Peters, S., Lepage, B., Cortot, A. B., Barlesi, F., Beau-Faller, M., Besse, B., Blons, H., Mansuet-Lupo, A., Urban, T., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.45.6095 · Cited by 668 · see citing works
Somatic mutations of epidermal growth factor receptor signaling pathway in lung cancers
Shigematsu, H., & Gazdar, A. F. (2005) · International Journal of Cancer · doi:10.1002/ijc.21496 · Cited by 658 · see citing works
“Recently, somatic mutations of HER2 TK domain were also reported in lung adenocarcinomas.(20,30) Of interest, HER2 mutations were of the same type and targeted the same region (30 of the aC-helix) in exon 20 as did EGFR in-frame duplications/insertions(20) (Figs.”
Background
Protein-tyrosine phosphatases and cancer
Östman, A., Hellberg, C. B., & Böhmer, F. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1837 · Cited by 657 · see citing works
Cancer genomics: from discovery science to personalized medicine
Chin, L., Andersen, J. N., & Futreal, P. A. (2011) · Nature Medicine · doi:10.1038/nm.2323 · Cited by 639 · see citing works
“and intragenic mutations in ERBB2 in non-small-cell lung cancer (NSCLC”
Background
Epidermal Growth Factor Receptor Mutations, Small-Molecule Kinase Inhibitors, and Non–Small-Cell Lung Cancer: Current Knowledge and Future Directions
Pao, W. J., & Miller, V. A. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.07.799 · Cited by 628 · see citing works
Cell line-based platforms to evaluate the therapeutic efficacy of candidate anticancer agents
Sharma, S. V., Haber, D. A., & Settleman, J. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2820 · Cited by 585 · see citing works
Ado-Trastuzumab Emtansine for Patients With HER2-Mutant Lung Cancers: Results From a Phase II Basket Trial
Li, B. T., Shen, R., Buonocore, D. J., Olah, Z. T., Ni, A., Ginsberg, M. S., Ulaner, G. A., Offin, M. D., Feldman, D., Hembrough, T., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.77.9777 · Cited by 557 · see citing works
Prevalence, Clinicopathologic Associations, and Molecular Spectrum of ERBB2 ( HER2 ) Tyrosine Kinase Mutations in Lung Adenocarcinomas
Arcila, M. E., Chaft, J. E., Nafa, K., Roy-Chowdhuri, S., Lau, C., Zaidinski, M., Paik, P. K., Zakowski, M. F., Kris, M. G., & Ladanyi, M. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-0912 · Cited by 505 · see citing works
BIM Mediates EGFR Tyrosine Kinase Inhibitor-Induced Apoptosis in Lung Cancers with Oncogenic EGFR Mutations
Costa, D. B., Halmos, B., Kumar, A., Schumer, S., Huberman, M. S., Boggon, T. J., Tenen, D. G., & Kobayashi, S. S. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040315 · Cited by 499 · see citing works
“Mutations in the analogous residue of ABL1 (L273M) and ErbB2 (L755S or P) (Figure 5C) have been described in patients with imatinib-resistant chronic myelogenous leukemia (CML) and solid tumors including gastric, breast, and lung cancers, respectively [35–37].”
Background
NF-κB addiction and its role in cancer: ‘one size does not fit all’
Chaturvedi, M., Sung, B., Yadav, V. R., Kannappan, R., & Aggarwal, B. B. (2010) · Oncogene · doi:10.1038/onc.2010.566 · Cited by 474 · see citing works
HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors
Wang, S. E., Narasanna, A., Pérez-Torres, M., Xiang, B., Wu, F. Y., Yang, S., Carpenter, G. F., Gazdar, A. F., Muthuswamy, S. K., & Arteaga, C. L. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.05.023 · Cited by 474 · see citing works
Somatic Mutations of the Protein Kinase Gene Family in Human Lung Cancer
Davies, H. R., Hunter, C., Smith, R., Stephens, P., Greenman, C., Bignell, G. R., Teague, J. W., Butler, A. P., Edkins, S., Stevens, C., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1855 · Cited by 464 · see citing works
Structural Analysis of the Mechanism of Inhibition and Allosteric Activation of the Kinase Domain of HER2 Protein
Aertgeerts, K., Skene, R. J., Yano, J. K., Sang, B., Zou, H., Snell, G., Jennings, A. J., Iwamoto, K., Habuka, N., Hirokawa, A., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.206193 · Cited by 448 · see citing works
Requirement for CDK4 kinase function in breast cancer
Yu, Q., Sicinska, E., Geng, Y., Ahnström, M., Zagozdzon, A., Kong, Y., Gardner, H., Kiyokawa, H., Harris, L. N., Stål, O., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2005.12.012 · Cited by 429 · see citing works
Herceptin: mechanisms of action and resistance
Nahta, R., & Esteva, F. J. (2005) · Cancer Letters · doi:10.1016/j.canlet.2005.01.041 · Cited by 446 · see citing works
Mutation analysis of 24 known cancer genes in the NCI-60 cell line set
Ikediobi, O. N., Davies, H. R., Bignell, G. R., Edkins, S., Stevens, C., O’Meara, S., Santarius, T., Avis, T., Barthorpe, S., Brackenbury, L., et al. (2006) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0433 · Cited by 433 · see citing works
“Gly(776) and the adjacent Val(777) are somatically mutated in gastric, lung, and colon cancers (29, 30).”
Background
Brigatinib combined with anti-EGFR antibody overcomes osimertinib resistance in EGFR-mutated non-small-cell lung cancer
Uchibori, K., Inase, N., Araki, M., Kamada, M., Sato, S., Okuno, Y., Fujita, N., & Katayama, R. (2017) · Nature Communications · doi:10.1038/ncomms14768 · Cited by 424 · see citing works
Cigarette smoking and lung cancer—relative risk estimates for the major histological types from a pooled analysis of case–control studies
Pesch, B., Kendzia, B., Gustavsson, P., Jöckel, K., Johnen, G., Pohlabeln, H., Olsson, A., Ahrens, W., Gross, I. M., Brüske, I., et al. (2012) · International Journal of Cancer · doi:10.1002/ijc.27339 · Cited by 509 · see citing works
“The greater the amount smoked, the greater the proportion of SqCC and SCLC relative to AdCa.”
BackgroundInfluential
Epidermal Growth Factor Receptor Mutations in Non–Small-Cell Lung Cancer: Implications for Treatment and Tumor Biology
Janne, P. A., Engelman, J. A., & Johnson, B. E. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.09.985 · Cited by 405 · see citing works
Genomic alterations in lung adenocarcinoma
Devarakonda, S. H. K., Morgensztern, D., & Govindan, R. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00077-7 · Cited by 398 · see citing works
IncreasedHER2Gene Copy Number Is Associated With Response to Gefitinib Therapy in Epidermal Growth Factor Receptor–Positive Non–Small-Cell Lung Cancer Patients
Cappuzzo, F., Varella-Garcia, M., Shigematsu, H., Domenichini, I., Bartolini, S., Ceresoli, G. L., Rossi, E., Ludovini, V., Gregorc, V., Toschi, L., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.09.111 · Cited by 369 · see citing works
Intrinsic and Acquired Resistance to HER2-Targeted Therapies in HER2 Gene-Amplified Breast Cancer: Mechanisms and Clinical Implications
Rexer, B. N., & Arteaga, C. L. (2012) · Critical Reviews™ in Oncogenesis · doi:10.1615/critrevoncog.v17.i1.20 · Cited by 372 · see citing works
Molecular biology of lung cancer.
Cooper, W. A., Lam, D. C.-L., O'Toole, S. A., & Minna, J. D. (2013) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2072-1439.2013.08.03 · Cited by 365 · see citing works
Update on Epidermal Growth Factor Receptor Mutations in Non–Small Cell Lung Cancer
Riely, G. J., Politi, K. A., Miller, V. A., & Pao, W. J. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0658 · Cited by 358 · see citing works
Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors
Tsurutani, J., Iwata, H., Krop, I. E., Janne, P. A., Doi, T., Takahashi, S., Park, H., Redfern, C. H., Tamura, K., Wise-Draper, T. M., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-1014 · Cited by 356 · see citing works
Advances in HER2-Targeted Therapy: Novel Agents and Opportunities Beyond Breast and Gastric Cancer
Meric‐Bernstam, F., Johnson, A. M., Dumbrava, E. E. I., Raghav, K. P. S., Balaji, K., Bhatt, M., Murthy, R. K., Rodon, J. A., & Piha-Paul, S. A. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2275 · Cited by 345 · see citing works
“Mutations are generally exon 20 in-frame insertions within the KD (20, 21, 29, 32).”
Background
Squamous Cell Carcinoma of the Lung: Molecular Subtypes and Therapeutic Opportunities
Perez-Moreno, P., Brambilla, E. M., Thomas, R. K., & Soria, J. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2370 · Cited by 347 · see citing works
Homozygous Deletions and Chromosome Amplifications in Human Lung Carcinomas Revealed by Single Nucleotide Polymorphism Array Analysis
Zhao, X., Weir, B. A., LaFramboise, T., Lin, M. G., Beroukhim, R., Garraway, L. A., Beheshti, J., Lee, J. C., Naoki, K., Richards, W. G., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4603 · Cited by 333 · see citing works
“Examples where identification of cancer-specific amplifications preceded the identification of cancer somatic mutations include PDGFRA (7, 8), EGFR (9–14), ERBB2 (15, 16), and PIK3CA (17–19).”
BackgroundInfluential
Making sense of cancer genomic dataPreprint
Chin, L., Hahn, W. C., Getz, G. A., & Meyerson, M. M. (2011) · Genes & Development · doi:10.1101/gad.2017311 · Cited by 336 · see citing works
Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors
Kris, M. G., Camidge, D. R., Giaccone, G., Hida, T., Li, B. T., O'Connell, J., Taylor, I., Zhang, H., Arcila, M. E., Goldberg, Z., et al. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv186 · Cited by 334 · see citing works
Clinicopathologic Features of Non-Small-Cell Lung Cancer with EML4–ALK Fusion Gene
Takahashi, T., Sonobe, M., Kobayashi, M., Yoshizawa, A., Menju, T., Nakayama, E., Mino, N., Iwakiri, S., Sato, K., Miyahara, R., et al. (2009) · Annals of Surgical Oncology · doi:10.1245/s10434-009-0808-7 · Cited by 326 · 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
Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: results from the European EUHER2 cohort
Mazières, J., Barlési, F., Filleron, T., Besse, B., Monnet, I., Beau‐Faller, M., Peters, S., Dansin, É., Früh, M., Pless, M., et al. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv573 · Cited by 323 · see citing works
Structure and Clinical Relevance of the Epidermal Growth Factor Receptor in Human Cancer
Kumar, A., Petri, E. T., Halmos, B., & Boggon, T. J. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.12.1178 · Cited by 308 · see citing works
Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance
Burgess, M. R., Skaggs, B. J., Shah, N. P., Lee, F. Y., & Sawyers, C. L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409770102 · Cited by 306 · see citing works
Translating insights from the cancer genome into clinical practice
Chin, L., & Gray, J. W. (2008) · Nature · doi:10.1038/nature06914 · Cited by 299 · see citing works
Genomics and the Continuum of Cancer Care
McDermott, U., Downing, J. R., & Stratton, M. R. (2011) · New England Journal of Medicine · doi:10.1056/nejmra0907178 · Cited by 294 · see citing works
New Targetable Oncogenes in Non–Small-Cell Lung Cancer
Oxnard, G. R., Binder, A. F., & Janne, P. A. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.42.9829 · Cited by 299 · see citing works
“2%) and were found to be nonoverlapping with KRAS and EGFR mutations.(31) A second study of 671 patients with resected NSCLC found HER2 mutations in 11 (1.”
Background
A Translational View of the Molecular Pathogenesis of Lung Cancer
Sato, M., Shames, D. S., Gazdar, A. F., & Minna, J. D. (2007) · Journal of Thoracic Oncology · doi:10.1097/01.jto.0000263718.69320.4c · Cited by 296 · see citing works
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
Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2
Greulich, H. E., Kaplan, B., Mertins, P., Chen, T.-H., Tanaka, K., Yun, C., Zhang, X., Lee, S., Cho, J., Ambrogio, L., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1203201109 · Cited by 279 · see citing works
“We have thus identified oncogenic somatic mutations of the extracellular domain of ERBB2 in lung and breast cancer, occurring at a rate of about 1%, approximately half that of the ERBB2 kinase domain mutations previously described in lung adenocarcinoma (12, 24, 26).”
Background
Acquired Resistance to Epidermal Growth Factor Receptor Kinase Inhibitors Associated with a Novel T854A Mutation in a Patient with EGFR-Mutant Lung Adenocarcinoma
Bean, J. M., Riely, G. J., Balak, M. N., Marks, J. L., Ladanyi, M., Miller, V. A., & Pao, W. J. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0151 · Cited by 276 · see citing works
Broad, Hybrid Capture–Based Next-Generation Sequencing Identifies Actionable Genomic Alterations in Lung Adenocarcinomas Otherwise Negative for Such Alterations by Other Genomic Testing Approaches
Drilon, A., Wang, L., Arcila, M. E., Balasubramanian, S., Greenbowe, J. R., Ross, J. S., Stephens, P., Lipson, D., Miller, V. A., Kris, M. G., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2683 · Cited by 274 · see citing works
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
“Studies of HER2 mutations in lung cancer showed association with Asian ethnicity, female gender, and non-smokers and with adenocarcinoma histology, particularly lepidic pattern [45–47].”
Background
Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu
Grève, J. D., Teugels, E., Geers, C., Decoster, L., Galdermans, D., Mey, J. D., Everaert, H., Umelo, I. A., Veld, P. I. '., & Schallier, D. C. C. (2012) · Lung Cancer · doi:10.1016/j.lungcan.2012.01.008 · Cited by 272 · see citing works
Receptor Tyrosine Kinase-Targeted Cancer Therapy
Yamaoka, T., Kusumoto, S., Ando, K., Ohba, M., & Ohmori, T. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113491 · Cited by 297 · see citing works
Targeting HER proteins in cancer therapy and the role of the non-target HER3
Hsieh, A. C., & Moasser, M. M. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6603910 · Cited by 269 · see citing works
“The mutational activation of HER2 is also seen in some cancers of the lung (Stephens et al, 2004).”
Background
Optimization of Patient Selection for Gefitinib in Non–Small Cell Lung Cancer by Combined Analysis of Epidermal Growth Factor Receptor Mutation, K-ras Mutation, and Akt Phosphorylation
Han, S., Kim, T., Jeon, Y. K., Hwang, P. G., Im, S., Lee, K.-H., Kim, J. H., Kim, D., Heo, D. S., Kim, N. K., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2845 · Cited by 250 · see citing works
Molecular Biology of Lung Cancer: Clinical Implications
Larsen, J. E., & Minna, J. D. (2011) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2011.08.003 · Cited by 247 · see citing works
Personalized Medicine in Non–Small-Cell Lung Cancer: Is KRAS a Useful Marker in Selecting Patients for Epidermal Growth Factor Receptor–Targeted Therapy?
Roberts, P. J., Stinchcombe, T. E., Der, C. J., & Socinski, M. A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.4365 · Cited by 240 · see citing works
LUNG CANCER PRENEOPLASIA
Wistuba, I. I., & Gazdar, A. F. (2006) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathol.1.110304.100103 · Cited by 232 · see citing works
Somatic Mutations of ERBB2 Kinase Domain in Gastric, Colorectal, and Breast Carcinomas
Lee, J. W., Soung, Y. H., Seo, S. H., Kim, S. Y., Park, C. H., Wang, Y. P., Park, K., Nam, S. W., Park, W. S., Kim, S. H., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-0976 · Cited by 228 · see citing works
“The earlier reports have found an ERBB2 mutation in a gastric cancer, but none in either breast or colorectal cancer (11, 12).”
BackgroundResultInfluential
Clinical cancer genomic profiling
Chakravarty, D., & Solit, D. B. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-021-00338-8 · Cited by 227 · see citing works
The challenge of NSCLC diagnosis and predictive analysis on small samples. Practical approach of a working group
Thunnissen, E., Kerr, K. M., Herth, F. J. F., Lantuéjoul, S., Papotti, M. G., Rintoul, R. C., Rossi, G., Skov, B. G., Weynand, B., Bubendorf, L., et al. (2011) · Lung Cancer · doi:10.1016/j.lungcan.2011.10.017 · Cited by 228 · see citing works

ERBB2 kinase mutations in lung-cancer tumours
Senior, K. (2004) · The Lancet Oncology · doi:10.1016/s1470-2045(04)01626-2 · Cited by 4 · see citing works
Absence of the ERBB2 kinase domain mutation in lung adenocarcinomas in Korean patients
Lee, J. W., Soung, Y. H., Kim, S. Y., Park, W. S., Nam, S. W., Kim, S. H., Lee, J. Y., Yoo, N. J., & Lee, S. H. (2005) · International Journal of Cancer · doi:10.1002/ijc.21113 · Cited by 5 · see citing works
ERBB3 kinase domain mutations are rare in lung, breast and colon carcinomas
Jeong, E. G., Soung, Y. H., Lee, J. W., Lee, S. H., Nam, S. W., Lee, J. Y., Yoo, N. J., & Lee, S. H. (2006) · International Journal of Cancer · doi:10.1002/ijc.22257 · Cited by 38 · see citing works
ERBB2 kinase domain mutation in the lung squamous cell carcinoma
Lee, J. W., Soung, Y. H., Kim, S. Y., Nam, S. W., Park, W. S., Wang, Y. P., Jo, K. H., Moon, S. W., Song, S. Y., Lee, J. Y., et al. (2005) · Cancer Letters · doi:10.1016/j.canlet.2005.05.026 · Cited by 47 · see citing works
A molecular chink in the lung cancer armour
Fong, K. M., & Bowman, R. (2004) · Respirology · doi:10.1111/j.1440-1843.2004.00672c.x

Authors: Stephens, P., Hunter, C., Bignell, G., Edkins, S., Davies, H., Teague, J., Stevens, C., O'Meara, S., Smith, R., Parker, A., Barthorpe, A., Blow, M., Brackenbury, L., Butler, A., Clarke, O., Cole, J., Dicks, E., Dike, A., Drozd, A., Edwards, K., Forbes, S., Foster, R., Gray, K., Greenman, C., Halliday, K., Hills, K., Kosmidou, V., Lugg, R., Menzies, A., Perry, J., Petty, R., Raine, K., Ratford, L., Shepherd, R., Small, A., Stephens, Y., Tofts, C., Varian, J., West, S., Widaa, S., Yates, A., Brasseur, F., Cooper, C. S., Flanagan, A. M., Knowles, M., Leung, S. Y., Louis, D. N., Looijenga, L. H. J., Malkowicz, B., Pierotti, M. A., Teh, B., Chenevix-Trench, G., Weber, B. L., Yuen, S. T., Harris, G., Goldstraw, P., Nicholson, A. G., Futreal, P. A., Wooster, R., & Stratton, M. R.
Affiliations: Wellcome Sanger Institute (GB)
Ludwig Cancer Research (BE)
Institute of Cancer Research (GB)
University College London (GB)
Cancer Research UK (GB)
Queen Mary Hospital (CN)
Massachusetts General Hospital (US)
Erasmus MC (NL)
University of Pennsylvania (US)
IFOM (IT)
Van Andel Institute (US)
Royal Brompton Hospital (GB)
Corresponding author: Futreal, P. Andrew
ORCID: Hunter, Chris
Edkins, Sarah
Davies, Helen
Teague, Jon
Blow, Matthew
Clarke, Oliver
Dicks, Ed
Foster, Rebecca
Gray, Kristian
Greenman, Chris
Raine, Keiran
Shepherd, Rebecca
Widaa, Sara
Yates, Andrew
Flanagan, Adrienne M.
Knowles, Margaret
Louis, David N.
Looijenga, Leendert H. J.
Pierotti, Marco A.
Teh, Bin
Yuen, Siu T.
Nicholson, Andrew G.
Futreal, P. Andrew
Stratton, Michael R.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2004-09
Volume: 431
Issue: 7008
Pages: 525-526
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/431525b
OpenAlex: W2049449785
Cited by: 802
References: 7
Citations by year: 2026: 14 · 2025: 25 · 2024: 19 · 2023: 20 · 2022: 31 · 2021: 41 · 2020: 26 · 2019: 26 · 2018: 34 · 2017: 30 · 2016: 20 · 2015: 45 · 2014: 61 · 2013: 46 · 2012: 40
FWCI: 48.46
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
UEA Digital Repository (University of East Anglia) (acceptedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
RePEc: Research Papers in Economics (submittedVersion)
DIAL (Catholic University of Leuven) (submittedVersion)
Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
UCL Discovery (University College London) (submittedVersion)
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: ERBB2, HER2, c-erbB-2, kinase domain mutations, intragenic mutations, lung cancer, lung adenocarcinoma
MeSH terms: Gefitinib, Carcinoma, Non-Small-Cell Lung, DNA Mutational Analysis, Enzyme Activation, Humans, Lung Neoplasms, Models, Molecular, Mutation, Neoplasms, Quinazolines, Protein Structure, Tertiary, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, ErbB Receptors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Intragenic ERBB2 kinase mutations in tumours

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks