Research
Human fetal neuroblast and neuroblastoma transcriptome analysis confirms neuroblast origin and highlights neuroblastoma candidate genes
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* Corresponding author: Frank Speleman franki.speleman@ugent.be
- † Equal contributors
1 Center for Medical Genetics, Ghent University Hospital, De Pintelaan, B-9000 Ghent, Belgium
2 Department of Medical Genetics, University Hospital Erasme, Lenniksebaan, B-1070 Brussels, Belgium
3 Division of Molecular Medicine, Department of Laboratory Medicine, Lund University, University Hospital MAS, SE-20502 Malmö, Sweden
4 Department of Pediatric Oncology and Hematology, University Hospital of Essen, Hufelandstr, Essen 45122, Germany
5 Children's Cancer Research Institute, University of Texas Health Science Center, Floyd Curl Drive, Mail Code 7784, San Antonio, Texas 78229-3900, USA
6 Department of Pediatrics, Ghent University Hospital, De Pintelaan, B-9000 Ghent, Belgium
7 Department of Pediatrics, UZ Gasthuisberg, Herestraat, B-3000 Leuven, Belgium
Genome Biology 2006, 7:R84 doi:10.1186/gb-2006-7-9-r84
Published: 21 September 2006Abstract
Background
Neuroblastoma tumor cells are assumed to originate from primitive neuroblasts giving rise to the sympathetic nervous system. Because these precursor cells are not detectable in postnatal life, their transcription profile has remained inaccessible for comparative data mining strategies in neuroblastoma. This study provides the first genome-wide mRNA expression profile of these human fetal sympathetic neuroblasts. To this purpose, small islets of normal neuroblasts were isolated by laser microdissection from human fetal adrenal glands.
Results
Expression of catecholamine metabolism genes, and neuronal and neuroendocrine markers in the neuroblasts indicated that the proper cells were microdissected. The similarities in expression profile between normal neuroblasts and malignant neuroblastomas provided strong evidence for the neuroblast origin hypothesis of neuroblastoma. Next, supervised feature selection was used to identify the genes that are differentially expressed in normal neuroblasts versus neuroblastoma tumors. This approach efficiently sifted out genes previously reported in neuroblastoma expression profiling studies; most importantly, it also highlighted a series of genes and pathways previously not mentioned in neuroblastoma biology but that were assumed to be involved in neuroblastoma pathogenesis.
Conclusion
This unique dataset adds power to ongoing and future gene expression studies in neuroblastoma and will facilitate the identification of molecular targets for novel therapies. In addition, this neuroblast transcriptome resource could prove useful for the further study of human sympathoadrenal biogenesis.