Despite a huge amount of research effort, the molecular mechanisms that underlie the transition from a "normal" cell to a cancerous cell are only poorly understood. After the discovery of the first cancer-causing genes or oncogenes and the finding that they are mutated forms of normal cellular genes, it was widely believed that a single mutation was enough to cause cancer. Subsequent research, however, has revealed that most cancers only develop as a result of several mutations. A bewildering variety of combinations of mutations have been shown to have the potential to give rise to cancer. Finding out which combinations are dangerous has to date been largely a matter of trial and error but this should change with the development of a tool to identify mutations that really do collaborate to cause cancer. Robert Eferl and colleagues announce the new "Multi-Hit" mouse in the current issue of the journal "Nature Methods". The work is one result of a longstanding collaboration between many institutions in the Vienna area coordinated by Mathias M-ller of the University of Veterinary Medicine, Vienna.
It is now generally accepted that cancer only arises if two or more genes are mutated. To date, learning which combinations of mutations cause cancer has represented an extremely laborious endeavour but the development of the "Multi-Hit" mouse looks set to change this. The group of Robert Eferl at the Ludwig Boltzmann Institute for Cancer Research, Vienna has taken advantage of the Cre-recombinase system to generate random combinations of correctly and incorrectly oriented oncogenes (or tumour suppressor genes, genes whose inactivation may contribute to the development of cancer) and investigated which of the combinations caused tumours.