ID2 expression in neuroblastoma does not correlate to MYCN levels and lacks prognostic value

Abstract

The MYCN proto-oncogene is frequently amplified in a subgroup of highly aggressive neuroblastomas. The molecular mechanism(s) by which the overexpressed MYCN contributes to an aggressive tumor cell behavior is not well understood. Recently, it was reported that the ID2 gene is a direct target for the MYCN and MYC transcription factors, and that ID2 expression and MYCN amplification correlate positively in neuroblastoma. In addition, ID2 expression was proposed as a negative prognostic parameter. As these results are of potential clinical importance, but not in agreement with our own initial observations, the putative correlation between ID2 and MYC(N) expression in neuroblastoma cell lines and tumors was reinvestigated. We found no correlation between MYCN and ID2 expression in neuroblastoma cell lines or tumor specimens. However, we did find a significant positive correlation between MYC and ID2 expressions in both MYCN-amplified and single-copy tumor specimens, and in MYCN single-copy cell lines. As previously reported, we also found an inverse correlation between MYC and MYCN expressions. Importantly, we could not confirm the reported prognostic power of ID2-expression in neuroblastoma. These data, obtained in two independent laboratories, challenge the previously proposed ID2-MYCN relation.

MYCN/c-MYC-induced microRNAs repress coding gene networks associated with poor outcome in MYCN/c-MYC-activated tumors

“…This additional separation suggests that MYCN/c-MYC signaling rather than MYCN levels alone underlies the differential expression of this miRNA signature. Indeed, c-MYC expression is Figure S2), confirming the inverse relationship between MYCN and c-MYC (Vandesompele et al, 2003), and has been shown to drive MYCN/c-MYC mRNA target gene expression in these tumors (Westermann et al, 2008). In addition, other genetic factors than increased MYCN/c-MYC activity could also contribute to the observed miRNA expression differences.…”

Expression of MYCN in pediatric synovial sarcoma

“…52 However, the prognostic significance of ID2 expression has been refuted by others, with some reporting no such association between ID2 expression and poor outcome in neuroblastomas and neuroblastoma cell lines. 53 The current study identified a group of synovial sarcomas with high levels of MYCN expression. Such overexpression was not seen in other sarcomas entering the differential diagnosis of synovial sarcoma, and provides evidence that testing for MYCN expression may be a useful ancillary investigation in the differentiation of pediatric-spindled and monomorphic sarcomas.…”

Targeting Id protein interactions by an engineered HLH domain induces human neuroblastoma cell differentiation

“…To test the impact of 13I expression, we took the two cell lines, LA-N-5 and SH-EP, which are N-and S-type, respectively, as models (Wainwright et al, 2001). N-MYC is amplified and overexpressed in LA-N-5, whereas it is barely detectable in SH-EP cells (Cohen et al, 1988;Vandesompele et al, 2003).…”

“…The most relevant for neuroblastoma is believed to be ID2, the most-highly expressed in this cancer (Perk et al, 2005). It is still controversial whether ID2 acts as N-MYC effector, the overexpression of which is found in a significant number of cases and predicts a poor outcome (Vandesompele et al, 2003;Schwab, 2004;Perk et al, 2005). Here, we report on Id inhibition in human neuroblastoma cells, obtained through a dominant interfering molecule, the HLH domain 13I (Ciarapica et al, 2003).…”