Researchers discover location of a testicular cancer gene

October 01, 1999

Olympic figure skater Scott Hamilton battled it, as did Tour de France champion Lance Armstrong. Testicular cancer is the most common tumor affecting young men and one of the most readily treated cancers. Although it clearly has genetic origins, this form of cancer has long-term recovery rate of greater than 95 percent.

The genetic basis for susceptibility to testicular cancer, as well as the basis for its extraordinary response to therapy, has been a mystery to scientists. Except for rare inherited mutations in families with the Li-Fraumeni syndrome (an inherited family trait carrying an increased risk of cancer during childhood and early adulthood), the identity of genes controlling susceptibility for testicular cancer is not known in either humans or in animals. Similar cancer susceptibility genes have already been found for many leukemias, breast, prostate, and many other cancers.

Scientists are narrowing in on the target, though. A group of Cleveland researchers have announced the discovery of the first link to a gene controlling inherited susceptibility to testicular cancer.

Led by Joseph Nadeau, the researchers uncovered evidence for susceptibility on mouse Chromosome 19. Nadeau is a professor of genetics at the Case Western Reserve University School of Medicine Department of Genetics and with University Hospitals of Cleveland's Center for Human Genetics and Ireland Cancer Center.

Their work, published in the October 1 issue of Nature Genetics, is based on research in 129/Sv mice, the only strain of mice to get spontaneous testicular cancer.

Using this strain, Nadeau and colleague Angabin Matin employed a new genetic technique of their own invention called chromosome substitution, where Chromosome 19 in 129/Sv mice was replaced with the corresponding chromosome from another mouse strain.

More than 80 percent of mice with the chromosome replacement had spontaneous testicular cancer by three weeks of age, demonstrating a strong testicular cancer susceptibility gene is located on Chromosome 19. (The corresponding gene in humans is located on chromosome segment 10q26.)

"The cancer results from a combination of genes in the host background and a gene on the substituted chromosome from the other strain," said Nadeau. "Most common human diseases have similar genetics, but are exceedingly hard to study because of the inherent complexity."

He added, "Chromosome substitution is a new and powerful way to simplify the analysis of many kinds of highly complex traits."

For Nadeau and colleagues, the search is now to discover the identity of this important new testicular cancer susceptibility gene. This new strain with its high frequency of testicular cancer is also the long-sought model for understanding the basis for the extraordinary response of testicular cancer to chemotherapies. These discoveries may lead to improved treatments of testicular and other cancers.

Case Western Reserve University

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