The Role of c-Met as a Biomarker and Player in Innate and Acquired Resistance in Non-Small-Cell Lung Cancer: Two New Mutations Warrant Further Studies
| العنوان: | The Role of c-Met as a Biomarker and Player in Innate and Acquired Resistance in Non-Small-Cell Lung Cancer: Two New Mutations Warrant Further Studies |
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| المؤلفون: | Marcello Tiseo, Godefridus J. Peters, Paul Germonpré, Christian Rolfo, Nele Van Der Steen, Christophe Hermans, Giulia Mazzaschi, Elisa Giovannetti, Karen Zwaenepoel, Daan P. Geerke, Patrick Pauwels, Paul Van Schil, Ken Op de Beeck, Filip Lardon, Rosa A. Luirink |
| المساهمون: | Medical oncology laboratory, AGEM - Re-generation and cancer of the digestive system, CCA - Imaging and biomarkers, AIMMS, Molecular and Computational Toxicology |
| المصدر: | Molecules Volume 24 Issue 24 Molecules: a journal of synthetic chemistry and natural product chemistry Molecules, 24(24). Multidisciplinary Digital Publishing Institute van der Steen, N, Zwaenepoel, K, Mazzaschi, G, A Luirink, R, P Geerke, D, op de Beeck, K, Hermans, C, Tiseo, M, van Schil, P, Lardon, F, Germonpré, P, Rolfo, C, Giovannetti, E, J Peters, G & Pauwels, P 2019, ' The Role of c-Met as a Biomarker and Player in Innate and Acquired Resistance in Non-Small-Cell Lung Cancer: Two New Mutations Warrant Further Studies ', Molecules, vol. 24, no. 24 . https://doi.org/10.3390/molecules24244443Test Molecules, 24(24):4443. Multidisciplinary Digital Publishing Institute (MDPI) Van Der Steen, N, Zwaenepoel, K, Mazzaschi, G, Luirink, R A, Geerke, D P, De Beeck, K O, Hermans, C, Tiseo, M, Van Schil, P, Lardon, F, Germonpré, P, Rolfo, C, Giovannetti, E, Peters, G J & Pauwels, P 2019, ' The role of c-met as a biomarker and player in innate and acquired resistance in non-small-cell lung cancer : Two new mutations warrant further studies ', Molecules, vol. 24, no. 24, 4443 . https://doi.org/10.3390/molecules24244443Test |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Lung Neoplasms, Mutant, Pharmaceutical Science, NSCLC, Analytical Chemistry, chemistry.chemical_compound, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Drug Discovery, Epidermal growth factor receptor, Neoplasm Metastasis, Receptor, 0303 health sciences, biology, Middle Aged, Proto-Oncogene Proteins c-met, 3. Good health, ErbB Receptors, Gene Expression Regulation, Neoplastic, Chemistry, Chemistry (miscellaneous), 030220 oncology & carcinogenesis, Molecular Medicine, Biomarker (medicine), Female, Antibody, Adult, C-Met, EGFR, Article, Deep sequencing, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Biomarkers, Tumor, medicine, Humans, Physical and Theoretical Chemistry, Lung cancer, Biology, Aged, 030304 developmental biology, business.industry, Organic Chemistry, Gene Amplification, medicine.disease, chemistry, Drug Resistance, Neoplasm, Mutation, biology.protein, Cancer research, Tumor Suppressor Protein p53, business, Biomarkers |
| الوصف: | The c-Met receptor is a therapeutically actionable target in non-small-cell lung cancer (NSCLC), with one approved drug and several agents in development. Most suitable biomarkers for patient selection include c-Met amplification and exon-14 skipping. Our retrospective study focused on the frequency of different c-Met aberrations (overexpression, amplification and mutations) in 153 primary, therapy-naï ve resection samples and their paired metastases, from Biobank@UZA. Furthermore, we determined the correlation of c-Met expression with clinicopathological factors, Epidermal Growth Factor Receptor (EGFR)-status and TP53 mutations. Our results showed that c-Met expression levels in primary tumors were comparable to their respective metastases. Five different mutations were detected by deep sequencing: three (E168D, S203T, N375S) previously described and two never reported (I333T, G783E). I333T, a new mutation in the Sema(phorin) domain of c-Met, might influence the binding of antibodies targeting the HGF-binding domain, potentially causing innate resistance. E168D and S203T mutations showed a trend towards a correlation with high c-Met expression (p = 0.058). We found a significant correlation between c-MET expression, EGFR expression (p = 0.010) and EGFR mutations (p = 0.013), as well as a trend (p = 0.057) with regards to TP53 mutant activity. In conclusion this study demonstrated a strong correlation between EGFR mutations, TP53 and c-Met expression in therapy-naï ve primary resection samples. Moreover, we found two new c-Met mutations that warrant further studies. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1420-3049 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d41c017861e5a2eba24b3519c13c0ba8Test https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85076355617&origin=inwardTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d41c017861e5a2eba24b3519c13c0ba8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14203049 |
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