GATA factors in human neuroblastoma: Distinctive expression patterns in clinical subtypes

Background:The aim of this study is to elucidate the expression patterns of GATA transcription factors in neuroblastoma and the developing sympathetic nervous system (SNS).Methods:GATA-2,-3 and-4 and their cofactor friend-of-GATA (FOG)-2 were investigated in primary neuroblastoma by immunohistochemistry, real-time RT-PCR (n73) and microarray analysis (n251). In addition, GATA-2,-3 and FOG-2 expression was determined by northern-blot hybridisation. In the developing murine SNS, Gata-4 and Fog-2 were examined by immunohistochemistry. Results:Although Gata-2,-3 and Fog-2 are expressed in the developing nervous system, Gata-4 was not detected. In contrast, protein expression of all factors was observed in human neuroblastoma. Northern-blot hybridisation and real-time RT-PCR suggested specific expression patterns of the four genes in primary neuroblastoma, but did not show unequivocal results. In the large cohort examined by microarrays, a significant association of GATA-2,-3 and FOG-2 expression with low-risk features was observed, whereas GATA-4 mRNA levels correlated with MYCN-amplification.Conclusion:The transcription factors GATA-2 and-3, which are essential for normal SNS development, and their cofactor FOG-2 are downregulated in aggressive but not in favourable neuroblastoma. In contrast, upregulation of GATA-4 appears to be a common feature of this malignancy and might contribute to neuroblastoma pathogenesis. © 2009 Cancer Research UK All rights reserved.