Analyses of FGFR3 and PIK3CA mutations in neuroblastomas and the effects of the corresponding inhibitors on neuroblastoma cell lines
| Autor: | Birthe K A Lange, Anna Ohmayer, Tina Dalianis, Ourania N. Kostopoulou, Malin Wickström, Teodora Andonova, Cinzia Bersani, Stefan Holzhauser |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Cancer Research Cell Survival Class I Phosphatidylinositol 3-Kinases Morpholines DNA Mutational Analysis Cell Aminopyridines Apoptosis Biology medicine.disease_cause Piperazines Neuroblastoma 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Humans Receptor Fibroblast Growth Factor Type 3 Child PI3K/AKT/mTOR pathway Cell Proliferation Phosphoinositide-3 Kinase Inhibitors Mutation Oncogene Imidazoles Infant Newborn Infant Cancer Cell cycle medicine.disease Molecular medicine 030104 developmental biology medicine.anatomical_structure Oncology Drug Resistance Neoplasm Fibroblast growth factor receptor Child Preschool 030220 oncology & carcinogenesis Benzamides Quinolines Cancer research Pyrazoles Female |
| Zdroj: | International Journal of Oncology. |
| ISSN: | 1791-2423 1019-6439 |
| Popis: | Fibroblast growth factor receptor (FGFR)3 and phosphatidylinositol‑4,5‑bisphosphate 3‑kinase, catalytic subunit alpha (PIK3CA) mutations are found in various types of cancer, such as urinary bladder cancer, human papillomavirus‑positive tonsillar and base of the tongue squamous cell carcinoma, breast cancer and some childhood sarcomas. Several drugs can target these genes, some of which have been used for the treatment of urinary bladder cancer. Much less is known about childhood cancer. For this reason, the present study investigated the presence of such mutations in neuroblastomas (NBs) and tested NB cell lines for sensitivity to FGFR and phosphoinositide 3‑kinase (PI3K) inhibitors. In total, 29 NBs were examined for the presence of the three most common FGFR3 and PIK3CA mutations using a competitive allele‑specific TaqMan PCR (CAST‑PCR). Furthermore, the SK‑N‑AS, SK‑N‑BE(2)‑C, SK‑N‑DZ, SK‑N‑FI and SK‑N‑SH NB cell lines (where SK‑N‑DZ had a deletion of PIK3C2G, none had FGFR mutations according to the Cancer Program's Dependency Map, but some were chemoresistant), were tested for sensitivity to FGFR (AZD4547) and PI3K (BEZ235 and BKM120) inhibitors by viability, cytotoxicity, apoptosis and proliferation assays. CAST‑PCR detected one FGFR3 mutation in 1/29 NBs. Following treatment with FGFR and PI3K inhibitors, a decrease in viability and proliferation was observed in the majority, but not all, the cell lines. Following combination treatment with both drugs, the sensitivity of all cell lines was increased. On the whole, the findings of this study demonstrate that FGFR3 and PIK3CA mutations are uncommon in patients with NB. However, certain NB cell lines are rather sensitive to both FGFR and PI3K inhibitors alone, and even more so when the different drugs are used in combination. |
| Databáze: | OpenAIRE |
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