GENE-EXPRESSION PROFILING OF ALVEOLAR RHABDOMYOSARCOMA WITH CDNA MICROARRAYS

Several forms of human sarcoma, lymphoma, and leukemia are characteriz ed by somatically acquired chromosome translocations that result in fu sion genes that encode chimeric transcription factors with oncogenic p roperties. We have used cDNA microarrays containing 1238 cDNAs to inve stigate the gene expression profile of a group of seven alveolar rhabd omyosarcoma (ARMS) cell lines characterized by the presence of the PAX 3-FKHR fusion gene. Using the method of multidimensional scaling to re present the relationships among the cell lines in two-dimensional Eucl idean space, we determined that ARMS cells show a consistent pattern o f 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 prima ry (PAX3-FKHR) and secondary (CDK4) genetic alterations in AIL-MS. The se results in ARMS demonstrate the potential of cDNA microarray techno logy to elucidate tumor-specific gene expression profiles in human can cers.