Assay May Help Identify New Genes that Predict Cancer Predisposition

The development of a new assay by researchers at UCLA's Jonsson Comprehensive Cancer Center may be useful in identifying genes that could predict a predisposition to cancer.

The team, led by Robert Schiestl, professor of pathology, radiation oncology and environmental health sciences, Jonsson Cancer Center, has uncovered a mechanism that “switches on” the genetic instability that is seen persistently in cancer cells.

The assay determines how well DNA’s repair mechanism works when there is a double-stranded break, which can lead to “genome rearrangements or deletions of certain genes that, when gone, result in cancer,” according to the researchers.

For the study, researchers irradiated cells and then “transformed them with a DNA fragment that detects the efficiency and the accuracy of double-strand break repair.” Because the DNA fragment was not irradiated, the researchers were able to show that the radiation activated a particular mechanism for double-stand break repairs in the fragment.

Even after “almost all of the DNA damage” caused in the cells by the radiation was repaired, the effect was still apparent, which shows that the mechanism induced by the radiation is separate from the actual damage the radiation caused.

The researchers were trying to determine if a double-stranded break in the DNA leads to damage that is contained to that particular area or if it can be seen elsewhere. The results of the study show that a break in one area has an “in-trans” effect—the damage could surface anywhere.

"What we have shown now in this paper is that DNA damage at one position in the genome, causes a certain mechanism of genetic instability all over the genome," Schiestl said. "Now we have to identify the mechanism of the pathway, identify the genes involved in inducing that pathway and that might give us targets that we can inhibit with drugs to try to reduce genetic instability. That could lead to a cancer treatment. Any time you can stop the growth of a cancer, you've won. It doesn't damage other tissues or spread to other organs. We might be able to stop the instability before it results in cancer."

Click here to review the study which was published in the April issue of Radiation Research.