Research article
Positional and functional mapping of a neuroblastoma differentiation gene on chromosome 11
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* Corresponding author: Katleen De Preter katleen.depreter@ugent.be
- † Equal contributors
1 Center for Medical Genetics, Ghent University Hospital MRB 2nd floor, De Pintelaan 185, B-9000 Ghent, Belgium
2 The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom
3 Department of Laboratory Medicine, Molecular Medicine, Lund University, University Hospital MAS, S-20502 Malmö, Sweden
4 Department of Pathological Anatomy, Ghent University Hospital BLOK A, De Pintelaan 185, B-9000 Ghent, Belgium
5 Sir Alastair Currie Cancer Research U.K. Laboratories, Division of Pathology, Molecular Medicine Centre, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, United Kingdom
BMC Genomics 2005, 6:97 doi:10.1186/1471-2164-6-97
Published: 6 July 2005Abstract
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 arrayCGH 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.
Conclusion
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.