Mousetrap for Cancer Genes

While cancers like leukemia stem from a multitude of errant genes, researchers can usually only decipher those defects one gene at a time. Now a new shortcut has accelerated the hunt for cancer genes by using a retrovirus that infects mice to flag otherwise hidden mines. The new strategy, described in this month's issue of Nature Genetics, marries gene sequencing with the techniques of traditional mouse genetics.

A team led by Neal Copeland and Nancy Jenkins of the National Cancer Institute in Frederick, Maryland, drew upon three strains of mice infected with a virus that predisposes the rodents to leukemia or lymphoma. The geneticists knew that the virus sneaks into and shuts down mouse genes at random. The difficult task was figuring out which insertions lead to malignant cancer. To do that, the team extracted the DNA from mouse tumors and hunted down the viral sequences. After some high-tech sequencing--which now can be done at breathtaking speeds--and double checking for sequences common to other tumors, the team came up with hundreds of candidates. They fed these sequences into DNA databases and struck upon matches pointing to more than 90 genes.

Some of these genes had already been linked to human malignancies and others, surprisingly, play roles in more distantly related processes such as cholesterol biosynthesis. Still others turned out to be snippets of orphan DNA with no designated function. What's more, the technique has turned up cancers caused by defects in genes working in cahoots; for example, the Myc and Pim1 mouse genes appear to lead to cancer. "It shows the power of the fusion between mouse genetics and model systems in genomics," says Copeland.

"The fact that they were able to deliver candidate cancer genes in a bushel like this, to me, is truly impressive," says cancer researcher Tyler Jacks at the Massachusetts Institute of Technology. Ahead lies the daunting task of validating whether all the novel genes do, in fact, cause cancer and if the technique can be applied to other kinds of malignancies, especially those that lead to solid tumors.