Chromosome changes in human cancer--are they pointers to mechanisms of initiation?

The identification of tumour-specific chromosome abnormalities in a wide range of malignancies together with an understanding of their role in the activation of proto-oncogenes and loss of tumour suppressor genes has resulted in chromosome analysis of malignant cells beginning to provide information on the etiology of different malignancies. Two principle types of translocation have been identified. In the first, a protooncogene becomes juxtaposed to the enhancing or controlling elements of an immunoglobulin or T-cell receptor gene, resulting in deregulation of proto-oncogene expression. The second type results when breaks occur within a gene on each chromosome, creating a fusion gene that encodes for a chimaeric protein, usually a transcription factor. Homozygosity for loss of tumour suppressor gene function is frequently achieved by the inherited or somatic mutation of one allele together with a chromosome deletion of the region containing the other allele. The increasing knowledge of the mechanisms involved in the formation of cancer-specific chromosome abnormalities should help elucidate the causative role of environmental mutagens such as radiation.