N-myc Oncogene RNA Expression in Neuroblastoma

Abstract

Tumor specimens from 33 patients with neuroblastoma were assayed for amplification of the N-myc oncogene and RNA expression to determine whether N-myc RNA expression levels correlated with N-myc gene amplification and clinical outcome. N-myc gene amplification was detected in one stage II tumor, one stage IV-S tumor, and seven stage III or IV tumors. In each case, N-myc RNA expression roughly paralleled N-myc gene amplification. However, enhanced N-myc RNA expression was not confined to tumors with N-myc gene amplification: all of the early (stage I and II) tumors, five stage IV-S tumors, and 12 advanced (stage III and IV) tumors had levels of N-myc RNA that were elevated up to 50-fold. While N-myc gene amplification correlated with prognosis, there was no such correlation with levels of N-myc RNA expression. The precise role of the N-myc gene in the pathogenesis of neuroblastoma remains unclear.

Expression of MYCN in pediatric synovial sarcoma

“…The lack of genomic amplification of MYCN in synovial sarcoma suggests alternative mechanisms are responsible for the high MYCN expression, such as alterations in transcriptional activity 37 or dysregulation of protein degradative pathways, as described in neuroblastoma. 38,39 In neuroblastoma, the clinical significance of high levels of MYCN expression without gene amplification remains controversial; some studies suggest no clinical significance, 40,41 whereas others have reported a significant association with poorer outcome in a subset of older patients but not in infants. 42 In the present series of synovial sarcoma, a high level of MYCN expression in the absence of MYCN amplification was not associated with a significant difference in local recurrence, metastatic rate or overall survival.…”

Co-amplification of a novel gene, NAG, with the N-myc gene in neuroblastoma

“…It is also noteworthy that some studies have shown that not all tumors with N-myc ampli®cation are associated with a bad prognosis; for example, 50% of stage II tumors with N-myc ampli®cation have a good outcome De Bernardi et al, 1995). Moreover, it has been demonstrated that increased N-myc expression seen in tumors that lack N-myc ampli®cation does not correlate with aggressive clinical behavior (Nisen et al, 1988;Slavc et al, 1990). This ®nding and the fact that the N-myc amplicon usually contains sequences extending much further than the N-myc gene suggests that other genes present were ampli®ed for N-myc and two of these (STA-NB-8 and IMR-32) were also ampli®ed for NAG as determined by Southern blot (Figure 3).…”

“…There is evidence that ampli®cation rather than up-regulation of basal expression is the main mechanism for the loss of auto-regulation of N-myc (Sivak et al, 1997) and for its over-expression (De Bernardi et al, 1995;Lutz and Schwab, 1997). However, it is not clear how N-myc ampli®cation results in poor outcome (Hiyama et al, 1991;Nisen et al, 1988;Slavc et al, 1990). It is possible that the co-ampli®cation of other DNA sequences may contribute to heterogeneity in the neuroblastoma phenotype.…”

Biology of tumors of the peripheral nervous system

“…However, in patients with single-copy tumors, there is not yet a biological marker or explanation why half of the remaining do not survive. A general correlation has been demonstrated between N-myc copy number and expression (Bartram and Berthold, 1987;Grady-Leopardi et al, 1986;Nisen et al, 1988;Seeger et al, 1988;Slavc et al, 1990). Also, it has been shown that a substantial number of tumors without N-myc amplification overexpress this gene, but single-copy tumors with high levels of N-myc expression do not appear to have a particularly poor outcome (Bartram and Berthold, 1987;Grady-Leopardi et al, 1986;Nisen et al, 1988;Seeger et al, 1988;Slavc et al, 1990).…”