Positional and functional mapping of a neuroblastoma differentiation gene on chromosome 11.
BACKGROUND
Loss of chromosome 11q defines a subset of high-stage aggressive neuroblastomas. Deletions are typically large and mapping efforts have thus far not lead to a well defined consensus region, which hampers the identification of positional candidate tumour suppressor genes. In a previous study, functional evidence for a neuroblastoma suppressor gene on chromosome 11 was obtained through microcell mediated chromosome transfer, indicated by differentiation of neuroblastoma cells with loss of distal 11q upon introduction of chromosome 11. Interestingly, some of these microcell hybrid clones were shown to harbour deletions in the transferred chromosome 11. We decided to further exploit this model system as a means to identify candidate tumour suppressor or differentiation genes located on chromosome 11.


RESULTS
In a first step, we performed high-resolution array CGH DNA copy-number analysis in order to evaluate the chromosome 11 status in the hybrids. Several deletions in both parental and transferred chromosomes in the investigated microcell hybrids were observed. Subsequent correlation of these deletion events with the observed morphological changes lead to the delineation of three putative regions on chromosome 11: 11q25, 11p13-->11p15.1 and 11p15.3, that may harbour the responsible differentiation gene.


CONCLUSIONS
Using an available model system, we were able to put forward some candidate regions that may be involved in neuroblastoma. Additional studies will be required to clarify the putative role of the genes located in these chromosomal segments in the observed differentiation phenotype specifically or in neuroblastoma pathogenesis in general.
Center for Medical Genetics, Ghent University Hospital, MRB 2nd floor, De Pintelaan 185, B-9000 Ghent, Belgium. katleen.depreter@ugent.be
Katleen
K
De Preter
Jo
J
Vandesompele
Björn
B
Menten
Philippa
P
Carr
Heike
H
Fiegler
Anders
A
Edsjö
Nigel P
NP
Carter
Nurten
N
Yigit
Wim
W
Waelput
Nadine
N
Van Roy
Scott
S
Bader
Sven
S
Påhlman
Frank
F
Speleman
D000483:Alleles; D002454:Cell Differentiation; D002460:Cell Line; D002872:Chromosome Deletion; D002874:Chromosome Mapping / Q000379:methods*; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure*; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018895:Microsatellite Repeats; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010590:Phalloidine / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D010590:Phalloidine