title: Human fetal neuroblast and neuroblastoma transcriptome analysis confirms neuroblast origin and highlights neuroblastoma candidate genes.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, De Pintelaan, B-9000 Ghent, Belgium.
authors.forename: Katleen
authors.initials: K
authors.lastname: De Preter
authors.forename: Jo
authors.initials: J
authors.lastname: Vandesompele
authors.forename: Pierre
authors.initials: P
authors.lastname: Heimann
authors.forename: Nurten
authors.initials: N
authors.lastname: Yigit
authors.forename: Siv
authors.initials: S
authors.lastname: Beckman
authors.forename: Alexander
authors.initials: A
authors.lastname: Schramm
authors.forename: Angelika
authors.initials: A
authors.lastname: Eggert
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Stallings
authors.forename: Yves
authors.initials: Y
authors.lastname: Benoit
authors.forename: Marleen
authors.initials: M
authors.lastname: Renard
authors.forename: Anne
authors.initials: A
authors.lastname: De Paepe
authors.forename: Geneviève
authors.initials: G
authors.lastname: Laureys
authors.forename: Sven
authors.initials: S
authors.lastname: Påhlman
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
mesh_terms: D030541:Databases, Genetic; D005333:Fetus / Q000166:cytology / Q000196:embryology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D009420:Nervous System / Q000196:embryology / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger