Human fetal neuroblast and neuroblastoma transcriptome analysis confirms neuroblast origin and highlights neuroblastoma candidate genes.
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.
De Preter
Katleen
K
Center for Medical Genetics, Ghent University Hospital, De Pintelaan, B-9000 Ghent, Belgium.
Vandesompele
Jo
J
Heimann
Pierre
P
Yigit
Nurten
N
Beckman
Siv
S
Schramm
Alexander
A
Eggert
Angelika
A
Stallings
Raymond L
RL
Benoit
Yves
Y
Renard
Marleen
M
De Paepe
Anne
A
Laureys
Geneviève
G
Påhlman
Sven
S
Speleman
Frank
F
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
D012333:RNA, Messenger