Genetic instability and darwinian selection in tumours (Reprinted from Trends in Biochemical Science, vol 12, Dec., 1999)

Genetic instability has Long been hypothesized to be a cardinal feature of cancer. Recent work has strengthened the proposal that mutational alteratio ns conferring instability occur early during tumour formation. The ensuing genetic instability drives tumour progression by generating mutations in on cogenes and tumour-suppressor genes. These mutant genes provide cancer cell s with a selective growth advantage, thereby Leading to the clonal outgrowt h of a tumour. Here, we discuss the role of genetic instability in tumour f ormation and outline future work necessary to substantiate the genetic inst ability hypothesis.