Khan J, Simon R, Bittner M, Chen Y, Leighton S B, Pohida T, Smith P D, Jiang Y, Gooden G C, Trent J M, Meltzer P S
Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA.
Cancer Res. 1998 Nov 15;58(22):5009-13.
Several forms of human sarcoma, lymphoma, and leukemia are characterized by somatically acquired chromosome translocations that result in fusion genes that encode chimeric transcription factors with oncogenic properties. We have used cDNA microarrays containing 1238 cDNAs to investigate the gene expression profile of a group of seven alveolar rhabdomyosarcoma (ARMS) cell lines characterized by the presence of the PAX3-FKHR fusion gene. Using the method of multidimensional scaling to represent the relationships among the cell lines in two-dimensional Euclidean space, we determined that ARMS cells show a consistent pattern of gene expression, which allows the cells to be clustered together. By searching across the seven ARMS cell lines, we found that 37 of 1238 genes were most consistently expressed in ARMS relative to a reference cell line. Only three of these genes have been previously reported to be expressed in ARMS. Among these 37 were genes related to both primary (PAX3-FKHR) and secondary (CDK4) genetic alterations in ARMS. These results in ARMS demonstrate the potential of cDNA microarray technology to elucidate tumor-specific gene expression profiles in human cancers.
几种形式的人类肉瘤、淋巴瘤和白血病的特征是体细胞获得性染色体易位，其导致融合基因，这些融合基因编码具有致癌特性的嵌合转录因子。我们使用了包含1238个cDNA的cDNA微阵列，来研究一组七个以存在PAX3-FKHR融合基因为特征的肺泡横纹肌肉瘤（ARMS）细胞系的基因表达谱。使用多维缩放方法在二维欧几里得空间中表示细胞系之间的关系，我们确定ARMS细胞显示出一致的基因表达模式，这使得细胞能够聚集在一起。通过在七个ARMS细胞系中进行搜索，我们发现相对于参考细胞系，1238个基因中的37个在ARMS中表达最为一致。这些基因中只有三个先前已报道在ARMS中表达。在这37个基因中，有与ARMS中的原发性（PAX3-FKHR）和继发性（CDK4）基因改变相关的基因。ARMS中的这些结果证明了cDNA微阵列技术在阐明人类癌症中肿瘤特异性基因表达谱方面的潜力。
