Frontiers in Oncology (Feb 2020)
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
- Kristyna Polaskova,
- Kristyna Polaskova,
- Tomas Merta,
- Tomas Merta,
- Alexandra Martincekova,
- Alexandra Martincekova,
- Danica Zapletalova,
- Danica Zapletalova,
- Michal Kyr,
- Michal Kyr,
- Pavel Mazanek,
- Zdenka Krenova,
- Peter Mudry,
- Marta Jezova,
- Jiri Tuma,
- Jarmila Skotakova,
- Ivana Cervinkova,
- Dalibor Valik,
- Dalibor Valik,
- Lenka Zdrazilova-Dubska,
- Lenka Zdrazilova-Dubska,
- Hana Noskova,
- Karol Pal,
- Ondrej Slaby,
- Pavel Fabian,
- Sarka Kozakova,
- Sarka Kozakova,
- Jakub Neradil,
- Jakub Neradil,
- Renata Veselska,
- Renata Veselska,
- Veronika Kanderova,
- Ondrej Hrusak,
- Tomas Freiberger,
- Tomas Freiberger,
- Tomas Freiberger,
- Giannoula Lakka Klement,
- Giannoula Lakka Klement,
- Jaroslav Sterba,
- Jaroslav Sterba,
- Jaroslav Sterba
Affiliations
- Kristyna Polaskova
- Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia
- Kristyna Polaskova
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia
- Tomas Merta
- Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia
- Tomas Merta
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia
- Alexandra Martincekova
- Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia
- Alexandra Martincekova
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia
- Danica Zapletalova
- Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia
- Danica Zapletalova
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia
- Michal Kyr
- Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia
- Michal Kyr
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia
- Pavel Mazanek
- Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia
- Zdenka Krenova
- Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia
- Peter Mudry
- Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia
- Marta Jezova
- Department of Pathology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia
- Jiri Tuma
- Department of Pediatric Surgery, Orthopedics and Traumatology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia
- Jarmila Skotakova
- Department of Pediatric Radiology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia
- Ivana Cervinkova
- Department of Pediatric Radiology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia
- Dalibor Valik
- Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czechia
- Dalibor Valik
- Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czechia
- Lenka Zdrazilova-Dubska
- Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czechia
- Lenka Zdrazilova-Dubska
- Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czechia
- Hana Noskova
- Central European Institute of Technology, Masaryk University, Brno, Czechia
- Karol Pal
- Central European Institute of Technology, Masaryk University, Brno, Czechia
- Ondrej Slaby
- Central European Institute of Technology, Masaryk University, Brno, Czechia
- Pavel Fabian
- Department of Oncological Pathology, Masaryk Memorial Cancer Institute, Brno, Czechia
- Sarka Kozakova
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia
- Sarka Kozakova
- Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czechia
- Jakub Neradil
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia
- Jakub Neradil
- 0Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czechia
- Renata Veselska
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia
- Renata Veselska
- 0Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czechia
- Veronika Kanderova
- 1Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czechia
- Ondrej Hrusak
- 1Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czechia
- Tomas Freiberger
- Central European Institute of Technology, Masaryk University, Brno, Czechia
- Tomas Freiberger
- 2Faculty of Medicine, Masaryk University, Brno, Czechia
- Tomas Freiberger
- 3Centre for Cardiovascular Surgery and Transplantation, Brno, Czechia
- Giannoula Lakka Klement
- Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia
- Giannoula Lakka Klement
- 4CSTS Health Care, Toronto, ON, Canada
- Jaroslav Sterba
- Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia
- Jaroslav Sterba
- International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia
- Jaroslav Sterba
- Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czechia
- DOI
- https://doi.org/10.3389/fonc.2019.01531
- Journal volume & issue
-
Vol. 9
Abstract
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.SummaryThe 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.
Keywords
