Unequivocal Delineation of Clinicogenetic Subgroups and Development of a New Model for Improved Outcome Prediction in Neuroblastoma
Open Access
- 1 April 2005
- journal article
- pediatric oncology
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 23 (10), 2280-2299
- https://doi.org/10.1200/jco.2005.06.104
Abstract
Purpose Neuroblastoma is a genetically heterogeneous pediatric tumor with a remarkably variable clinical behavior ranging from widely disseminated disease to spontaneous regression. In this study, we aimed for comprehensive genetic subgroup discovery and assessment of independent prognostic markers based on genome-wide aberrations detected by comparative genomic hybridization (CGH). Materials and Methods Published CGH data from 231 primary untreated neuroblastomas were converted to a digitized format suitable for global data mining, subgroup discovery, and multivariate survival analyses. Results In contrast to previous reports, which included only a few genetic parameters, we present here for the first time a strategy that allows unbiased evaluation of all genetic imbalances detected by CGH. The presented approach firmly established the existence of three different clinicogenetic subgroups and indicated that chromosome 17 status and tumor stage were the only independent significant predictors for patient outcome. Important new findings were: (1) a normal chromosome 17 status as a delineator of a subgroup of presumed favorable-stage tumors with highly increased risk; (2) the recognition of a survivor signature conferring 100% 5-year survival for stage 1, 2, and 4S tumors presenting with whole chromosome 17 gain; and (3) the identification of 3p deletion as a hallmark of older age at diagnosis. Conclusion We propose a new regression model for improved patient outcome prediction, incorporating tumor stage, chromosome 17, and amplification/deletion status. These findings may prove highly valuable with respect to more reliable risk assessment, evaluation of clinical results, and optimization of current treatment protocols.Keywords
This publication has 37 references indexed in Scilit:
- Genetic parameters of neuroblastomasCancer Letters, 2002
- Neuroblastoma tumour genetics: clinical and biological aspectsJournal of Clinical Pathology, 2001
- Neuroblastomas with chromosome 11q loss and single copy MYCN comprise a biologically distinct group of tumours with adverse prognosisBritish Journal of Cancer, 2001
- Allelic deletion at 11q23 is common in MYCN single copy neuroblastomasOncogene, 1999
- Molecular Biology of NeuroblastomaJournal of Clinical Oncology, 1999
- Gain of Chromosome Arm 17q and Adverse Outcome in Patients with NeuroblastomaThe New England Journal of Medicine, 1999
- Loss of heterozygosity of 3p markers in neuroblastoma tumours implicate a tumour-suppressor locus distal to the FHIT geneBritish Journal of Cancer, 1998
- Clinical relevance of tumor cell ploidy and N-myc gene amplification in childhood neuroblastoma: a Pediatric Oncology Group study.Journal of Clinical Oncology, 1991
- Loss of heterozygosity for the short arm of chromosome 1 in human neuroblastomas: correlation with N-myc amplification.Proceedings of the National Academy of Sciences of the United States of America, 1989
- Association of Multiple Copies of the N-mycOncogene with Rapid Progression of NeuroblastomasThe New England Journal of Medicine, 1985