Advanced search
1 file | 5.04 MB Add to list

Identification of a novel HER3 activating mutation homologous to EGFR-L858R in lung cancer

(2015) ONCOTARGET. 7(3). p.3068-3083
Author
Organization
Abstract
Somatic mutations found within the tyrosine kinase domain (TKD) of the human epidermal growth factor (HER) family of receptors have been implicated in the development and progression of non-small cell lung cancer (NSCLC). However, no conclusive reports have described pathogenic mutations in kinase-impaired HER3. Here, we report a case of an advanced chemotherapy-resistant NSCLC, harboring a novel HER3(V855A) somatic mutation homologous to the EGFR(L858R)activating mutation. Co-expression of HER3(V855A) and wild-type HER2 enhances ligand-induced transformation of murine and human cell lines, while HER-targeted inhibitors potently suppress mutant HER3 activity. Consistent with these observations, in silico computational modeling predicts that mutant V855A alters the kinase domain and c-terminal end of the HER3 protein. Taken together, these findings provide a basis for the clinical exploration of targeted therapies in HER3 mutant NSCLC and by extrapolation, in other cancers that more frequently carry somatic HER3 mutations.
Keywords
lung cancer, HER3 kinase mutation, HER inhibitor, HER3-V855A, GROWTH-FACTOR RECEPTOR, TYROSINE KINASE INHIBITORS, AFATINIB BIBW 2992, SOMATIC MUTATIONS, DOMAIN MUTATION, OPEN-LABEL, ERBB3, GEFITINIB, EGFR, BREAST

Downloads

  • 663-Umelo et al.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 5.04 MB

Citation

Please use this url to cite or link to this publication:

MLA
Umelo, Ijeoma et al. “Identification of a Novel HER3 Activating Mutation Homologous to EGFR-L858R in Lung Cancer.” ONCOTARGET 7.3 (2015): 3068–3083. Print.
APA
Umelo, I., Noeparest, A., Chen, G., Renard, M., Geers, C., Van Steenkiste, J., Giron, P., et al. (2015). Identification of a novel HER3 activating mutation homologous to EGFR-L858R in lung cancer. ONCOTARGET, 7(3), 3068–3083.
Chicago author-date
Umelo, Ijeoma, Amir Noeparest, Gang Chen, Marleen Renard, Caroline Geers, Johan Van Steenkiste, Philippe Giron, Olivier De Wever, Erik Teugels, and Jacques De Grève. 2015. “Identification of a Novel HER3 Activating Mutation Homologous to EGFR-L858R in Lung Cancer.” Oncotarget 7 (3): 3068–3083.
Chicago author-date (all authors)
Umelo, Ijeoma, Amir Noeparest, Gang Chen, Marleen Renard, Caroline Geers, Johan Van Steenkiste, Philippe Giron, Olivier De Wever, Erik Teugels, and Jacques De Grève. 2015. “Identification of a Novel HER3 Activating Mutation Homologous to EGFR-L858R in Lung Cancer.” Oncotarget 7 (3): 3068–3083.
Vancouver
1.
Umelo I, Noeparest A, Chen G, Renard M, Geers C, Van Steenkiste J, et al. Identification of a novel HER3 activating mutation homologous to EGFR-L858R in lung cancer. ONCOTARGET. 2015;7(3):3068–83.
IEEE
[1]
Ijeoma Umelo et al., “Identification of a novel HER3 activating mutation homologous to EGFR-L858R in lung cancer,” ONCOTARGET, vol. 7, no. 3, pp. 3068–3083, 2015.
@article{8515597,
  abstract     = {Somatic mutations found within the tyrosine kinase domain (TKD) of the human epidermal growth factor (HER) family of receptors have been implicated in the development and progression of non-small cell lung cancer (NSCLC). However, no conclusive reports have described pathogenic mutations in kinase-impaired HER3. Here, we report a case of an advanced chemotherapy-resistant NSCLC, harboring a novel HER3(V855A) somatic mutation homologous to the EGFR(L858R)activating mutation. Co-expression of HER3(V855A) and wild-type HER2 enhances ligand-induced transformation of murine and human cell lines, while HER-targeted inhibitors potently suppress mutant HER3 activity. Consistent with these observations, in silico computational modeling predicts that mutant V855A alters the kinase domain and c-terminal end of the HER3 protein. Taken together, these findings provide a basis for the clinical exploration of targeted therapies in HER3 mutant NSCLC and by extrapolation, in other cancers that more frequently carry somatic HER3 mutations.},
  author       = {Umelo,  Ijeoma and Noeparest, Amir and Chen, Gang and Renard, Marleen and Geers, Caroline and Van Steenkiste, Johan and Giron, Philippe and De Wever, Olivier and Teugels, Erik and De Grève, Jacques},
  issn         = {1949-2553},
  journal      = {ONCOTARGET},
  keywords     = {lung cancer,HER3 kinase mutation,HER inhibitor,HER3-V855A,GROWTH-FACTOR RECEPTOR,TYROSINE KINASE INHIBITORS,AFATINIB BIBW 2992,SOMATIC MUTATIONS,DOMAIN MUTATION,OPEN-LABEL,ERBB3,GEFITINIB,EGFR,BREAST},
  language     = {eng},
  number       = {3},
  pages        = {3068--3083},
  title        = {Identification of a novel HER3 activating mutation homologous to EGFR-L858R in lung cancer},
  url          = {http://dx.doi.org/10.18632/oncotarget.6585},
  volume       = {7},
  year         = {2015},
}

Altmetric
View in Altmetric
Web of Science
Times cited: