It is increasingly recognised that recessive mutations play an important role in the pathogenesis of many forms of malignancy. Some of the affected loci may prove to be recessively-activated proto-oncogenes, but others are now known to be tumorigenic solely by virtue of their loss or inactivation and therefore form a distinct and novel family of tumour genes. Preliminary evidence suggests that such genes are likely to be functionally heterogeneous and to encode molecules involved in the inhibition of cellular proliferation and/or the induction of differentiation. Their further study is likely to illuminate fundamental mechanisms of normal cellular growth and differentiation as well as having important implications for the pathogenesis and management of cancer.

The fusion of a Rous sarcoma virus (RSV)-transformed rat fibroblast clone to at least 2 different human cell types reproducibly produces phenotypically normal hybrids. Analysis of such hybrids reveals that proviral silence is the result of transcriptional down-regulation, presumably by a trans-acting human molecule. Furthermore, this phenomenon seems to be strongly influenced by the proviral chromosomal integration site and its imposition may entail a mechanism that is required only transiently.