Individual patient risk stratification of high‐risk neuroblastomas using a two‐gene score suited for clinical use |
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| Authors: | Kristoffer von Stedingk Katleen De Preter Jo Vandesompele Rosa Noguera Ingrid Øra Jan Koster Rogier Versteeg Sven Påhlman David Lindgren Håkan Axelson |
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| Affiliation: | 1. Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden;2. Department of Pediatric Oncology and Hematology, Sk?ne University Hospital, Lund University, Lund, Sweden;3. Center for Medical Genetics, Department of Pediatrics and Genetics, Ghent University, Ghent, Belgium;4. Department of Pathology, Medical School, University of Valencia, Valencia, Spain;5. Department of Oncogenomics, Academic Medical Center, Amsterdam, The Netherlands |
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| Abstract: | Several gene expression‐based prognostic signatures have been described in neuroblastoma, but none have successfully been applied in the clinic. Here we have developed a clinically applicable prognostic gene signature, both with regards to number of genes and analysis platform. Importantly, it does not require comparison between patients and is applicable amongst high‐risk patients. The signature is based on a two‐gene score (R‐score) with prognostic power in high‐stage tumours (stage 4 and/or MYCN‐amplified diagnosed after 18 months of age). QPCR‐based and array‐based analyses of matched cDNAs confirmed cross platform (array‐qPCR) transferability. We also defined a fixed cut‐off value identifying prognostically differing subsets of high‐risk patients on an individual patient basis. This gene expression signature independently contributes to the current neuroblastoma classification system, and if prospectively validated could provide further stratification of high‐risk patients, and potential upfront identification of a group of patients that are in need of new/additional treatment regimens. |
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| Keywords: | neuroblastoma prognosis high‐risk R‐score |
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