title: Individual patient risk stratification of high-risk neuroblastomas using a two-gene score suited for clinical use.
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.
authors: Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.|Department of Pediatric Oncology and Hematology, Skåne University Hospital, Lund University, Lund, Sweden.
authors: Kristoffer
authors: K
authors: von Stedingk
authors: Center for Medical Genetics, Department of Pediatrics and Genetics, Ghent University, Ghent, Belgium.
authors: Katleen
authors: K
authors: De Preter
authors: Center for Medical Genetics, Department of Pediatrics and Genetics, Ghent University, Ghent, Belgium.
authors: Jo
authors: J
authors: Vandesompele
authors: Department of Pathology, Medical School, University of Valencia, Valencia, Spain.
authors: Rosa
authors: R
authors: Noguera
authors: Department of Pediatric Oncology and Hematology, Skåne University Hospital, Lund University, Lund, Sweden.
authors: Ingrid
authors: I
authors: Øra
authors: Department of Oncogenomics, Academic Medical Center, Amsterdam, The Netherlands.
authors: Jan
authors: J
authors: Koster
authors: Department of Oncogenomics, Academic Medical Center, Amsterdam, The Netherlands.
authors: Rogier
authors: R
authors: Versteeg
authors: Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
authors: Sven
authors: S
authors: Påhlman
authors: Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
authors: David
authors: D
authors: Lindgren
authors: Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
authors: Håkan
authors: H
authors: Axelson
mesh_terms: D014408:Biomarkers, Tumor; D002675:Child, Preschool; D055088:Early Detection of Cancer; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D000071447:N-Myc Proto-Oncogene Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D011379:Prognosis; D059467:Transcriptome / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins
keywords: R-score; high-risk; neuroblastoma; prognosis