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  • Title: Temporally regulated neural crest transcription factors distinguish neuroectodermal tumors of varying malignancy and differentiation.
    Author: Gershon TR, Oppenheimer O, Chin SS, Gerald WL.
    Journal: Neoplasia; 2005 Jun; 7(6):575-84. PubMed ID: 16036108.
    Abstract:
    Neuroectodermal tumor cells, like neural crest (NC) cells, are pluripotent, proliferative, and migratory. We tested the hypothesis that genetic programs essential to NC development are activated in neuroectodermal tumors. We examined the expression of transcription factors PAX3, PAX7, AP-2alpha, and SOX10 in human embryos and neuroectodermal tumors: neurofibroma, schwannoma, neuroblastoma, malignant nerve sheath tumor, melanoma, medulloblastoma, supratentorial primitive neuroectodermal tumor, and Ewing's sarcoma. We also examined the expression of P0, ERBB3, and STX, targets of SOX10, AP-2alpha, and PAX3, respectively. PAX3, AP-2alpha, and SOX10 were expressed sequentially in human NC development, whereas PAX7 was restricted to mesoderm. Tumors expressed PAX3, AP-2alpha, SOX10, and PAX7 in specific combinations. SOX10 and AP-2alpha were expressed in relatively differentiated neoplasms. The early NC marker, PAX3, and its homologue, PAX7, were detected in poorly differentiated tumors and tumors with malignant potential. Expression of NC transcription factors and target genes correlated. Transcription factors essential to NC development are thus present in neuroectodermal tumors. Correlation of specific NC transcription factors with phenotype, and with expression of specific downstream genes, provides evidence that these transcription factors actively influence gene expression and tumor behavior. These findings suggest that PAX3, PAX7, AP-2alpha, and SOX10 are potential markers of prognosis and targets for therapeutic intervention.
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