Chromosome Translocations Generating Chimeric Transcription Factors, Unique Genetic Events with Pleiotropic Cellular Consequences

The observation that chromosome rearrangements detected in tumor cells are frequently specific and recurrent within a defined tumor type has long suggested they play a fundamental role in the initiation and/or progression of the tumorigenic process. Among these rearrangements, over a hundred different balanced and reciprocal translocations have been described, mainly in hematopoietic malignancies and mesenchymal tumors (Mitelman, 1994). Over the past 10 years, a large number of these translocations has been characterized at the molecular level (reviewed in Rabbitts, 1994). They can result in the transcriptional deregulation of a gene without alteration of its coding sequence, a situation frequently observed in translocations of B- or T-cell malignancies where transcriptional deregulation of a proto-oncogene is brought about by its juxtaposition to immunoglobulin chain or T-cell receptor loci. Alternatively, translocations can lead to gene fusions resulting in the synthesis of chimeric proteins.