Schwab M, Varmus H E, Bishop J M, Grzeschik K H, Naylor S L, Sakaguchi A Y, Brodeur G, Trent J
Nature. 1984;308(5956):288-91. doi: 10.1038/308288a0.
Cellular oncogenes comprise a class of genes whose aberrant expression or function may be involved in the development of tumours. Indeed, several naturally occurring animal and human tumours are associated with consistent alterations in the structure or genomic position of particular cellular oncogenes. Recently, we isolated a DNA segment having limited similarity to c-myc (termed N-myc) from a human neuroblastoma cell line. Although N-myc was present as a single copy in normal cells, it was selectively amplified up to 140-fold in tumour cells from human neuroblastomas. Now, we have used somatic cell hybrids to show that N-myc is normally localized on the distal short arm of chromosome 2, and in situ hybridization to localize N-myc to chromosome 2p23-24. Further, in situ hybridization localizes amplified N-myc in neuroblastoma cells to homogeneously staining regions (HSRs) on different chromosomes. Thus, our results suggest that amplification and translocation of N-myc may be interrelated processes associated with human neuroblastoma, and demonstrate that the site of N-myc amplification is quite variable and bears no apparent relationship to either the normal single-copy locus or recognized sites of non-random chromosome alteration in human neuroblastoma.
细胞癌基因包括一类基因,其异常表达或功能可能与肿瘤的发生发展有关。事实上,几种天然存在的动物和人类肿瘤与特定细胞癌基因的结构或基因组位置的一致性改变有关。最近,我们从人神经母细胞瘤细胞系中分离出一段与c-myc具有有限相似性的DNA片段(称为N-myc)。虽然N-myc在正常细胞中以单拷贝形式存在,但在人神经母细胞瘤的肿瘤细胞中它被选择性扩增至140倍。现在,我们利用体细胞杂种证明N-myc正常定位于2号染色体的远端短臂,并通过原位杂交将N-myc定位于2p23-24。此外,原位杂交将神经母细胞瘤细胞中扩增的N-myc定位于不同染色体上的均匀染色区(HSRs)。因此,我们的结果表明N-myc的扩增和易位可能是与人类神经母细胞瘤相关的相互关联的过程,并证明N-myc扩增的位点变化很大,与人类神经母细胞瘤中正常的单拷贝基因座或公认的非随机染色体改变位点均无明显关系。