Prospects for cancer genetics

A number of distinct strategies have been used over the past two decades to uncover the genes involved in tumorigenesis. Their use raises the questions of whether we will require novel approaches in order to continue the progress of cancer genetics. Retrovirus mediated transduction of proto-oncogenes and transfection of tumour associated oncogenes are both inefficient ways of uncovering oncogenes, each being encumbered by technical obstacles that limit their utility. Improvements in the gene transfer strategy may yield a host of new oncogenes. New cloning techniques may have a role here as well as in revealing the existence of genes that are amplified in tumour cell genomes. The major technique for uncovering novel tumour suppressor genes--detection of loss of heterozygosity--is also limited in its sensitivity to detecting genes that are lost in large numbers of tumours. The techniques for uncovering these genes through analysis of pedigrees in which mutant versions of these genes are passed through the germline are encumbered by issues of penetrance and the complexities associated with the inheritance of polygenic traits. In both instances, improvements in data acquisition and analysis will reveal tumour suppressor genes that have proved elusive until now. Over the next decade, we will learn much about how the defects in another apparatus--that responsible for the maintenance of genomic integrity--contribute to cancer susceptibility. Beyond these genes lie yet others about which we seem to know little at present--those that induce the last stages of cancer including invasiveness and metastasis. These will represent an entirely new cohort of genes to be uncovered over the next decade.