In this week's journal Nature, researchers report finding the first gene responsible for inherited susceptibility of testicular cancer in mice. The Ter mutation occurs in a gene called dead end, which is involved in normal testicular development and which may play a role in inherited forms of a testicular cancer occurring in infants.
The mutation causes a huge increase in testicular cancer incidence, from 5 percent to 94 percent. Although this dramatic rise was described in a mouse strain more than 30 years ago, it has taken until now for the identity of the gene itself to be discovered.
These results suggest that the Ter mutation may adversely affect essential aspects of primordial germ cell biology, and the authors explain that the work will have important implications for understanding of the genetic control of testicular germ cell tumors.
"Dead end is the earliest acting genetic defect that leads to these tumors," said Joseph Nadeau, Ph.D., a co-senior author of the paper and the Jewell Professor and Chair of Genetics at the Case Western Reserve University School of Medicine. "Interestingly, this defect causes these mice to develop tumors during fetal development. The mutation in the dead end gene increases susceptibility nearly 20 fold and is therefore one of the most potent inherited cancer genes," he said.
The researchers say that the gene appears to be involved in controlling RNA editing, which is a poorly understood process to change the RNA sequence in specific ways to build proteins.
"For the first time, we know the identity of one of the genes that controls inherited susceptibility. This gene and other functionally related genes might be used to diagnose at-risk individuals for more careful monitoring. And perhaps by understanding the role of RNA editing in the biology of the cancer stem cells we can develop improved therapeutics to treat and perhaps prevent these cancers,"said Nadeau.