Comprehensive Molecular Profiling for Relapsed/Refractory Pediatric Burkitt Lymphomas-Retrospective Analysis of Three Real-Life Clinical Cases-Addressing Issues on Randomization and Customization at the Bedside.

Autor:	Polaskova K; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia.; International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia., Merta T; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia.; International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia., Martincekova A; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia.; International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia., Zapletalova D; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia.; International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia., Kyr M; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia.; International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia., Mazanek P; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia., Krenova Z; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia., Mudry P; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia., Jezova M; Department of Pathology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia., Tuma J; Department of Pediatric Surgery, Orthopedics and Traumatology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia., Skotakova J; Department of Pediatric Radiology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia., Cervinkova I; Department of Pediatric Radiology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia., Valik D; Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czechia.; Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czechia., Zdrazilova-Dubska L; Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czechia.; Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czechia., Noskova H; Central European Institute of Technology, Masaryk University, Brno, Czechia., Pal K; Central European Institute of Technology, Masaryk University, Brno, Czechia., Slaby O; Central European Institute of Technology, Masaryk University, Brno, Czechia., Fabian P; Department of Oncological Pathology, Masaryk Memorial Cancer Institute, Brno, Czechia., Kozakova S; International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia.; Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czechia., Neradil J; International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia.; Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czechia., Veselska R; International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia.; Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czechia., Kanderova V; Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czechia., Hrusak O; Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czechia., Freiberger T; Central European Institute of Technology, Masaryk University, Brno, Czechia.; Faculty of Medicine, Masaryk University, Brno, Czechia.; Centre for Cardiovascular Surgery and Transplantation, Brno, Czechia., Klement GL; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia.; CSTS Health Care, Toronto, ON, Canada., Sterba J; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia.; International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia.; Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czechia.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2020 Feb 07; Vol. 9, pp. 1531. Date of Electronic Publication: 2020 Feb 07 (Print Publication: 2019).
DOI:	10.3389/fonc.2019.01531
Abstrakt:	In order to identify reasons for treatment failures when using targeted therapies, we have analyzed the comprehensive molecular profiles of three relapsed, poor-prognosis Burkitt lymphoma cases. All three cases had resembling clinical presentation and histology and all three patients relapsed, but their outcomes differed significantly. The samples of their tumor tissue were analyzed using whole-exome sequencing, gene expression profiling, phosphoproteomic assays, and single-cell phosphoflow cytometry. These results explain different treatment responses of the three histologically identical but molecularly different tumors. Our findings support a personalized approach for patient with high risk, refractory, and rare diseases and may contribute to personalized and customized treatment efforts for patients with limited treatment options like relapsed/refractory Burkitt lymphoma. Summary: The main aim of this study is to analyze three relapsed Burkitt lymphoma patients using a comprehensive molecular profiling, in order to explain their different outcomes and to propose a biomarker-based targeted treatment. In cases 1 and 3, the tumor tissue and the host were analyzed prospectively and appropriate target for the treatment was successfully implemented; however, in case 2, analyses become available only retrospectively and his empirically based rescue treatment did not hit the right target of his disease. (Copyright © 2020 Polaskova, Merta, Martincekova, Zapletalova, Kyr, Mazanek, Krenova, Mudry, Jezova, Tuma, Skotakova, Cervinkova, Valik, Zdrazilova-Dubska, Noskova, Pal, Slaby, Fabian, Kozakova, Neradil, Veselska, Kanderova, Hrusak, Freiberger, Klement and Sterba.)
Databáze:	MEDLINE
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