Abstract
Neuroblastoma is a heterogeneous tumour with a variety of clinical phenotypes, ranging
from a localised tumour with excellent outcome (stage 1) to a metastatic, usually
fatal malignancy (stage 4). In order to investigate the genetic relationship between
these tumour subtypes, a loss of heterozygosity (LOH) analysis was carried out. Composite
LOH allelotypes incorporating data from 96 loci on 5 chromosomes (1p, 3p, 4p, 11q,
14q), were constructed for 62 neuroblastomas. Neuroblastomas with similar allelotypes
were clustered into groups and allelotype patterns correlated with clinical features.
Three distinct genetic subgroups of neuroblastoma were observed. The largest group
(50% of tumours) was characterised by specific allelotype patterns indicative of a
stepwise accumulation of genetic alterations (11q LOH → 1p, 4p, and/or 14q LOH → 3p LOH), associated with progression from low to high stage disease. These tumours
are distinct from MYCN amplified neuroblastomas which have a more rapid and aggressive disease course, and
also a proportion of low stage tumours, often ganglioneuromas or ganglioneuroblastomas,
with restricted growth potential.
Keywords
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Article info
Publication history
Accepted:
March 15,
2006
Received in revised form:
February 27,
2006
Received:
November 15,
2005
Footnotes
☆Supported by research grants from SPARKS (CMM, SAC), the United Birmingham Hospitals’ Endowment Fund (CMM, TG) and the Children’s Cancer and Leukaemia Research Fund of the Birmingham Children’s Hospital (CMM).
Identification
Copyright
© 2006 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
