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Distinct evolutionary mechanisms for genomic imbalances in high-risk and low-risk neuroblastomas

Gisselsson Nord, David LU ; Lundberg, Gisela LU ; Øra, Ingrid LU and Höglund, Mattias LU (2007) In Journal of Carcinogenesis 6. p.15-15
Abstract
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... (More)
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) whole-chromosome 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Carcinogenesis
volume
6
pages
15 - 15
publisher
Medknow Publications and Media Pvt. Ltd
external identifiers
  • pmid:17897457
  • scopus:35649009816
ISSN
0974-6773
DOI
10.1186/1477-3163-6-15
language
English
LU publication?
yes
id
4799ec44-15a8-41b4-8f24-9dc39c67b24c (old id 1138433)
alternative location
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2042979&rendertype=abstract
date added to LUP
2008-08-19 11:44:03
date last changed
2017-04-09 04:31:44
@article{4799ec44-15a8-41b4-8f24-9dc39c67b24c,
  abstract     = {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) whole-chromosome 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.},
  author       = {Gisselsson Nord, David and Lundberg, Gisela and Øra, Ingrid and Höglund, Mattias},
  issn         = {0974-6773},
  language     = {eng},
  pages        = {15--15},
  publisher    = {Medknow Publications and Media Pvt. Ltd},
  series       = {Journal of Carcinogenesis},
  title        = {Distinct evolutionary mechanisms for genomic imbalances in high-risk and low-risk neuroblastomas},
  url          = {http://dx.doi.org/10.1186/1477-3163-6-15},
  volume       = {6},
  year         = {2007},
}