Tumour suppressor genes: oncogenesis update

Evidence for tumour suppressor genes (anti-oncogenes, hemerogenes, flatogenes) has been obtained from the behaviour of familial childhood tumours in man, tumours in Drosophila caused by recessive mutations, experiments on fusing tumour cells to normal cells in tissue culture and revertants of oncogene-transformed cells. They may comprise more than one class of genes, one of which is likely to consist of genes responsible for normal differentiation. In large long-lived animals like man, which have a large potential somatic mutational load, mutant genes are associated with autosomal dominant behaviour in families. The susceptible individuals inherit heterozygosity of the tumour gene but the emergence of a tumour appears to follow a second somatic mutational event which results in homozygosity or hemizygosity. Hence, in tumour cells the mutations behave in a recessive manner. Success in isolating the normal genes may provide new tools for antenatal diagnosis of carriers and open up the possibility of developing new gene therapy.