George R E, Kenyon R M, McGuckin A G, Malcolm A J, Pearson A D, Lunec J
Department of Child Health, Medical School, University of Newcastle upon Tyne, UK.
Oncogene. 1996 Apr 4;12(7):1583-7.
Although N-myc amplification is strongly associated with a poor prognosis, not all patients with neuroblastomas having N-myc amplification fare badly. To investigate whether genes other than N-myc are responsible for contributing to the prognosis, we examined seven cell lines and 87 primary tumours for co-amplification of candidate genes known to be present near the normal N-myc locus: ornithine decarboxylase (ODC), ribonucleotide reductase (RRM2), syndecan-1 and a DEAD box protein gene, DDX1. Sequence analysis of the pG21 cDNA clone previously reported to represent an expressed gene frequently co-amplified with N-myc, showed this to be from the DDX1 gene. No co-amplification with the first three genes was found in any of the cell lines or tumour samples. DDX1, however was found to be amplified along with N-myc in 4/6 (67%) cell lines and 6/16 (38%) of the N-myc amplified tumours. Co-amplification of DDX1 and N-myc was found more frequently in stage 4 or 4S tumours than lower stage (1-3) tumours. With the exclusion of a single 4S case, there was a highly significant reduction in the mean disease-free interval from 24.4 +/- 4.7 (SE, n = 10) months for cases with co-amplification of N-myc and DDX1 compared with 9.2 +/- 1.8 (SE, n = 5) months for those cases showing amplification of N-myc alone (P = 0.0056, Welch's unpaired t-test). No amplification of DDX1, ODC, RRM2, or syndecan-1 was found in the absence of N-myc amplification. These observation indicate that the N-myc amplicon is of varied size and/or position relative to the N-myc gene, with DDX1 representing at least one other gene frequently co-amplified with N-myc. Further studies are required to confirm the biological and prognostic significance of DDX1 co-amplification and to elucidate the role that DDX1 plays in tumour genesis and progression.
尽管N - myc基因扩增与预后不良密切相关，但并非所有患有N - myc基因扩增的神经母细胞瘤患者预后都很差。为了研究除N - myc基因外的其他基因是否对预后有影响，我们检测了7个细胞系和87个原发性肿瘤，以寻找已知位于正常N - myc基因座附近的候选基因的共扩增情况：鸟氨酸脱羧酶（ODC）、核糖核苷酸还原酶（RRM2）、多配体蛋白聚糖 - 1和一个DEAD盒蛋白基因DDX1。对先前报道的代表一个经常与N - myc基因共扩增的表达基因的pG21 cDNA克隆进行序列分析，结果显示该基因来自DDX1基因。在任何细胞系或肿瘤样本中均未发现与前三个基因的共扩增情况。然而，在4/6（67%）的细胞系和6/16（38%）的N - myc基因扩增肿瘤中发现DDX1与N - myc基因同时扩增。与较低分期（1 - 3期）肿瘤相比，在4期或4S期肿瘤中更频繁地发现DDX1和N - myc基因的共扩增。排除一个单独的4S期病例后，N - myc和DDX1共扩增病例的平均无病间期从24.4±4.7（标准误，n = 10）个月显著缩短至9.2±1.8（标准误，n = 5）个月（P = 0.0056，Welch非配对t检验），而单独显示N - myc基因扩增的病例为9.2±1.8（标准误，n = 5）个月。在没有N - myc基因扩增的情况下，未发现DDX1、ODC、RRM2或多配体蛋白聚糖 - 1的扩增。这些观察结果表明，相对于N - myc基因，N - myc扩增子的大小和/或位置各不相同，DDX1代表至少另一个经常与N - myc基因共扩增的基因。需要进一步研究来证实DDX1共扩增的生物学和预后意义，并阐明DDX1在肿瘤发生和进展中所起的作用。
