Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors
| Autor: | Jeremias Wohlschlaeger, Aggeliki Rapti, Georgia Trakada, Konstantinos Porpodis, Daniel C. Christoph, Wolfgang Hohenforst-Schmidt, Robert Werner, Fabian Dominik Mairinger, Adamidis, Mairinger T, Schmidt Kw, Claudia Vollbrecht, Robert Fred Henry Walter, Elena Flom, P. Zarogoulidis, Kollmeier J, Jan Schmeller |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Carcinoid tumors Medizin lung cancer Biology Neuroendocrine tumors 600 Technik Medizin angewandte Wissenschaften::610 Medizin und Gesundheit Neuroendocrine differentiation 03 medical and health sciences 0302 clinical medicine CDKN2A medicine NanoString Lung cancer personalized therapy Massive parallel sequencing biomarkers medicine.disease 030104 developmental biology Oncology 030220 oncology & carcinogenesis Monoclonal biology.protein Cancer research Mdm2 next-generation sequencing Research Paper |
| Zdroj: | Journal of Cancer |
| Popis: | Background: Lung cancer is the leading cause of cancer-related deaths worldwide. 25% show neuroendocrine differentiation (typical/atypical carcinoids, large-/small-cell neuroendocrine carcinomas). Carcinoids present with long survival rates, but metastatic carcinoids correlate with decreased survival and are commonly insensitive to standard chemotherapy or radiation. Therefore, novel therapeutic strategies are urgently needed. Material and methods: 70 representative tumor specimens were used for next-generation sequencing analysis of 14 genes related to therapy response. Additionally, mRNA-expression profiles of 60 matching samples were determined for 13 selected drug targets by using the NanoString nCounter technology. Results: A number of features known to sensitize tumors for different targeted therapies could be identified, which hopefully improve the clinical management of this subgroup of lung neoplasias. In particular, EGFR expression was observed in the investigated tumors in a noteworthy manner. Additionally, MDM2 was strongly expressed in the majority of all samples whereas the expression of its physiological inhibitor, CDKN2A, was nearly absent in all low-grade tumors. TP53 showed a high frequency of variants in high-grade tumors but mutations were rare in carcinoids. Conclusion: Based on our results, therapeutic approaches with MDM2-inhibitors and monoclonal anti-EGFR antibodies may be promising in pulmonary carcinoid tumors. CA extern |
| Databáze: | OpenAIRE |
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