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Analysis of candidate gene co-amplification with MYCN in neuroblastoma

Lookup NU author(s): Dr Rebecca Kenyon, Professor Andrew Pearson, Professor John LunecORCiD


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Previous studies have revealed that the MYCN gene spans approximately 7 kb, while the amplicon has been estimated to be 100 kb to 1 Mb long [1-3]. This implies that several other genes may be present on the MYCN amplicon. Such co-amplified genes could contribute to the malignant phenotype and might provide an explanation for why not all patients with MYCN amplification have a poor outcome. We investigated 7 neuroblastoma cell lines and 167 primary tumours for the co-amplification of candidate genes known to be present near the MYCN locus: ornithine decarboxylase, ribonucleotide reductase, syndecan-1 and a DEAD box protein gene, DDX1. We also investigated further the pG21 expressed sequence previously reported to be co-amplified with MYCN. No co-amplification with the first 3 genes was found in any of the cell lines or tumour samples. DDX1 was found to be amplified along with MYCN in 4/6 (67%) cell lines and 18/38 (47%) of the MYCN amplified tumours. No amplification of DDX1, ODC1, RRM2 or syndecan-1 was found in the absence of MYCN amplification. DDX1 co-amplification was observed to occur mainly in stage 4 or 4S patients. With the exclusion of those with 4S disease, patients with DDX1 co-amplification had a significantly shorter mean (+/-SE) disease-free interval (4.1 +/- 1.4, n = 8 months) compared with patients with MYCN amplification alone (19.6 +/- 4.5, n = 17) (P = 0.04, Welch's unpaired t-test). The pG21 sequence was identical to part of the DDX1 gene. These observations indicate that there is at least 1 other gene co-amplified with MYCN in a proportion of cases and that those patients with DDX1 co-amplification tend to relapse more quickly. It also implies that the MYCN amplicon is of varied size and/or position relative to the MYCN gene. (C) 1997 Elsevier Science Ltd.

Publication metadata

Author(s): George RE, Kenyon R, McGuckin AG, Kohl N, Kogner P, Christiansen H, Pearson ADJ, Lunec J

Publication type: Article

Publication status: Published

Journal: European Journal of Cancer

Year: 1997

Volume: 33

Issue: 12

Pages: 2037-2042

Print publication date: 01/10/1997

ISSN (print): 0959-8049

ISSN (electronic): 1879-0852

Publisher: Pergamon


DOI: 10.1016/S0959-8049(97)00206-2


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