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- Title
Distinct evolutionary mechanisms for genomic imbalances in high-risk and low-risk neuroblastomas.
- Authors
Gisselsson, David; Lundberg, Gisela; Øra, Ingrid; Höglund, Mattias
- Abstract
Background: Neuroblastoma (NB) is the most common extracranial solid tumour of childhood. Several genomic imbalances correlate to prognosis in NB, with structural rearrangements, including gene amplification, in a near-diploid setting typically signifying high-risk tumours and numerical changes in a near-triploid setting signifying low-risk tumours. Little is known about the temporal sequence in which these imbalances occur during the carcinogenic process. Methods: We have reconstructed the appearance of cytogenetic imbalances in 270 NBs by first grouping tumours and imbalances through principal component analysis and then using the number of imbalances in each tumour as an indicator of evolutionary progression. Results: Tumours clustered in four sub-groups, dominated respectively by (1) gene amplification in double minute chromosomes and few other aberrations, (2) gene amplification and loss of 1p sequences, (3) loss of 1p and other structural aberrations including gain of 17q, and (4) wholechromosome gains and losses. Temporal analysis showed that the structural changes in groups 1-3 were acquired in a step-wise fashion, with loss of 1p sequences and the emergence of double minute chromosomes as the earliest cytogenetic events. In contrast, the gains and losses of whole chromosomes in group 4 occurred through multiple simultaneous events leading to a near-triploid chromosome number. Conclusion: The finding of different temporal patterns for the acquisition of genomic imbalances in high-risk and low-risk NBs lends strong support to the hypothesis that these tumours are biologically diverse entities, evolving through distinct genetic mechanisms.
- Subjects
NEUROBLASTOMA; NERVOUS system tumors; TUMORS; MEDICAL research; CARCINOGENESIS
- Publication
Journal of Carcinogenesis, 2007, Vol 6, Issue 1, p15
- ISSN
0974-6773
- Publication type
Article
- DOI
10.1186/1477-3163-6-15