Identification of a putative transcriptome signature common to neuroblastoma and neural crest cells

Abstract

Neuroblastoma, the most common extracranial tumor in children, is caused by genetic lesions in neural crest precursors of the peripheral nervous system. However, since neural crest cells are neither present after birth and nor are they readily accessible for analysis, very little is known about the genetic networks they might share with neuroblastoma cells during their development, despite their common embryonic origin. Here we have developed a novel resource for lineage tracing and for the isolation of neural crest cells in the chick embryo, enabling us to perform a genome-wide expression screen in neural crest progenitors. In this analysis, we efficiently retrieved known neural crest specific genes that validate our screening strategy and we identified new genes that participate in diverse cell activities, yet with a strong representation of genes associated to cell signaling and cell mobility, two hallmarks of migratory cells. We crossed this transcriptome data with that in the neuroblastoma gene server to search for the human orthologues of these genes associated with neuroblastoma. Accordingly, we retrieved 54 genes expressed strongly in both populations, from which we were able to validate a total of 27 genes expressed in the neural crest that are relevant to neuroblastoma formation. We propose that neural crest and neuroblastoma tumor cells share a common genetic signature that might serve to characterize neuroblastoma cancer stem cells, thereby contributing to the identification of specific targets against which new therapeutic strategies can be designed.