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ID2 Expression Is not Associated with MYCN Amplification or Expression in Human Neuroblastomas¹

Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104 [Q. W., G. H., S. S., Y. M., C. L. W., C. G., M. D. H., J. M. M.]; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 [S. S., E. R., M. D. H., J. M. M.]; and Division of Biostatistics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104 [H. Z.]

MYCN is a biologically and clinically important oncogene in human neuroblastoma as genomic amplification reliably predicts for aggressive tumor behavior and a poor prognosis. However, the mechanism by which MYCN amplification and overexpression contributes to a highly malignant phenotype remains obscure. ID2 is a dominant inhibitor of the RB1 tumor suppressor gene product and recently was suggested to be a direct transcriptional target of MYCN. Overexpression of Id2 protein has thus been postulated to result in functional inactivation of retinoblastoma in MYCN-amplified neuroblastomas, offering a potential explanation for the undifferentiated and highly proliferative nature of most MYCN-amplified neuroblastomas, as well as the paucity of retinoblastoma pathway mutations observed in clinical samples. We therefore sought to determine the likelihood that ID2 overexpression is associated with MYCN amplification and overexpression in human neuroblastoma. ID2 was not differentially expressed in 39 primary neuroblastoma specimens analyzed by oligonucleotide array-based expression analysis, and there was no correlation with MYCN expression levels. ID2 mRNA and protein expression was highly variable and independent of MYCN amplification status and mRNA expression in 10 human-derived neuroblastoma cell lines. In addition, ID2 mRNA expression was not associated with MYCN gene amplification status (P = 0.15) or MYCN expression (r = 0.22) in 131 separate diagnostic primary neuroblastoma samples analyzed by real-time quantitative RT-PCR. These data suggest that transcriptional regulation of ID2 by the MycN oncoprotein is unlikely to be a seminal molecular event resulting in a highly malignant neuroblastoma phenotype.

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