Genes Proximal and Distal to MYCN Are Highly Expressed in Human Neuroblastoma as Visualized by Comparative Expressed Sequence Hybridization

Abstract

MYCN amplification is associated with poor prognosis in neuroblastoma disease. To improve our understanding of the influence of the MYCN amplicon and its corresponding expression, we investigated the 2p expression pattern of MYCN amplified (n ‫؍‬ 13) and nonamplified (n ‫؍‬ 4) cell lines and corresponding primary tumors (n ‫؍‬ 3) using the comparative expressed sequence hybridization technique. All but one MYCN amplified cell line displayed overexpression at 2p. Expression peaks were observed frequently at 2pter and less frequently at 2p24 (MYCN locus), 2p23.3-23.2, and/or 2p23.1. Importantly, cell lines and two corresponding primary tumors displayed expression peaks at similar loci. No significant 2p24 expression level was observed for those cell lines displaying a low amplification rate (n ‫؍‬ 3) by comparative genomic hybridization. Only the cell lines with an enhanced peak at 2p23.2-23.3 displayed coamplification of the ALK gene (2p23.2), reported to be associated with unfavorable prognosis. Finally, two of four cell lines without MYCN amplification, both derived from patients with poor outcome, also showed an expression peak at 2p23.2. These data indicate that, besides MYCN, other genes proximal and distal to MYCN are highly expressed in neuroblastoma. The prognostic significance of expression peaks at 2p23.2-23.3, independent of MYCN and ALK status, remains to be investigated.

2p24 Gain Region Harboring MYCN Gene Compared with MYCN Amplified and Nonamplified Neuroblastoma

“…54 In addition, genes proximal and distal to MYCN were found to be highly expressed when using comparative expressed sequence hybridization. 55 We, too, failed to detect any significant correlation between MYCN status and MYCN expression levels (P ϭ 0.637; Table 4). …”

Gene amplification as double minutes or homogeneously staining regions in solid tumors: Origin and structure

“…The occurrence of coamplification of genes originating from different chromosomes is not a rare event in hematological amplifications (Frascella et al 2000;Morel et al 2003;Graux et al 2004;Martin-Subero et al 2005;Van Roy et al 2006). Amplicons with a complex pattern have been reported also in studies utilizing fresh cancer material and analyzed using array-CGH technology (Beheshti et al 2003;Caren et al 2008;Fix et al 2008;Stock et al 2008). Gibaud et al (2010) documented, in a glioma case, dmin derived from four different chromosomal domains.…”

“…STA-NB cell lines were provided by Cold Spring Harbor Laboratory Press on May 8, 2018 -Published by genome.cshlp.org Downloaded from P.F. Ambros, and some of them have been previously described (Ambros et al 1997;Narath et al 2007;Stock et al 2008). STA-NB-10/hsr and STA-NB-10/dmin are subclones of the same cell line, showing MYCN [v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)] amplification in form of hsr or dmin, respectively.…”

Outcome of the p53-mediated DNA damage response in neuroblastoma is determined by morphological subtype and MYCN expression

“…11,12 The MYCN gene spans less than 10 kb, yet the amplicon size varies between different tumors, ranging from 350 kb to 8 Mb. 13 Several genes have been reported to be co-amplified with MYCN including include DDX1, ODC and NAG. 14,15 Our previous work reported a correlation between MYCN amplification and a failure to G 1 arrest following irradiation induced DNA damage in wild-type p53 neuroblastoma cell lines as well as distinct differences in cellular response to DNA damage in MYCN-amplified and non-MYCN amplified cells; 16,17 however, siRNA mediated knockdown of MYCN in 2 MYCN amplified neuroblastoma cell lines did not restore a G 1 arrest.…”