» Articles » PMID: 16989664

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.

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.

Citing Articles

A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations.

Saldana-Guerrero I, Montano-Gutierrez L, Boswell K, Hafemeister C, Poon E, Shaw L Nat Commun. 2024; 15(1):3745.

PMID: 38702304 PMC: 11068915. DOI: 10.1038/s41467-024-47945-7.


Targeting the myeloid microenvironment in neuroblastoma.

Stip M, Teeuwen L, Dierselhuis M, Leusen J, Krijgsman D J Exp Clin Cancer Res. 2023; 42(1):337.

PMID: 38087370 PMC: 10716967. DOI: 10.1186/s13046-023-02913-9.


Analysis of High-Risk Neuroblastoma Transcriptome Reveals Gene Co-Expression Signatures and Functional Features.

Martinez-Pacheco M, Hernandez-Lemus E, Mejia C Biology (Basel). 2023; 12(9).

PMID: 37759629 PMC: 10525871. DOI: 10.3390/biology12091230.


IgA antibody immunotherapy targeting GD2 is effective in preclinical neuroblastoma models.

Stip M, Evers M, Nederend M, Chan C, Reiding K, Damen M J Immunother Cancer. 2023; 11(7).

PMID: 37479484 PMC: 10364159. DOI: 10.1136/jitc-2023-006948.


Neural crest-related NXPH1/α-NRXN signaling opposes neuroblastoma malignancy by inhibiting organotropic metastasis.

Fanlo L, Gomez-Gonzalez S, Rozalen C, Perez-Nunez I, Sangrador I, Tomas-Daza L Oncogene. 2023; 42(28):2218-2233.

PMID: 37301928 DOI: 10.1038/s41388-023-02742-2.


References
1.
Dentice M, Bandyopadhyay A, Gereben B, Callebaut I, Christoffolete M, Kim B . The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate. Nat Cell Biol. 2005; 7(7):698-705. PMC: 1761694. DOI: 10.1038/ncb1272. View

2.
Zhang B, Kirov S, Snoddy J . WebGestalt: an integrated system for exploring gene sets in various biological contexts. Nucleic Acids Res. 2005; 33(Web Server issue):W741-8. PMC: 1160236. DOI: 10.1093/nar/gki475. View

3.
Tai A, Mak W, Ng P, Chua D, Ng M, Fu L . High-throughput loss-of-heterozygosity study of chromosome 3p in lung cancer using single-nucleotide polymorphism markers. Cancer Res. 2006; 66(8):4133-8. DOI: 10.1158/0008-5472.CAN-05-2775. View

4.
Nakayama K, Nakayama K . Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer. 2006; 6(5):369-81. DOI: 10.1038/nrc1881. View

5.
Wang Q, Diskin S, Rappaport E, Attiyeh E, Mosse Y, Shue D . Integrative genomics identifies distinct molecular classes of neuroblastoma and shows that multiple genes are targeted by regional alterations in DNA copy number. Cancer Res. 2006; 66(12):6050-62. DOI: 10.1158/0008-5472.CAN-05-4618. View