Jefferson and Kimmel Cancer Center Scientists Find New Link Between FHIT Gene and Hereditary Colon Cancer

Crystal structure of the worm protein, NitFhit. Work by Jefferson Medical College (JMC) and Kimmel Cancer Center has established links connecting mutations in the human FHIT gene to many human cancers including lung and hereditary colorectal cancer. The figure is courtesy of Helen C. Pace, PhD, Postdoctoral Research Fellow, and Charles Brenner, PhD, Associate Professor of Microbiology and Immunology, JMC.

Researchers at Jefferson Medical College (JMC) have unexpectedly found evidence indicating that the recently identified FHIT gene may play a role in a common form of hereditary colorectal cancer.

Scientists already suspect the FHIT gene, when damaged, may contribute to a number of cancers, such as esophageal, gastric, kidney, breast and lung.

Now, the new evidence linking the gene to hereditary colorectal cancer may help scientists better understand the mechanisms of all the cancers previously identified with the gene.

A team of JMC and Kimmel Cancer Center researchers, led by Kay Huebner, PhD, Professor of Microbiology and Immunology, reported their new findings in the Proceedings of the National Academy of Sciences. The researchers had set out to study genetically altered laboratory mice which lacked the FHIT gene. In the course of that research, Dr. Huebner's team found that mice with damaged FHIT genes developed symptoms resembling those associated with forms of hereditary colorectal cancer.

FHIT as "Gatekeeper"
The finding adds new support to the Jefferson researchers' belief that the FHIT gene, when healthy, "is a so-called gatekeeper that helps prevent carcinogen-caused tumors," explains Dr. Huebner.

Understanding FHIT's role in preventing the cancer-causing effects of a carcinogen may be paramount if researchers are going to develop ways to treat or prevent disease.

In 1996, Dr. Huebner, in collaboration with Carlo M. Croce, MD, Director of the Kimmel Cancer Center and Professor and Chairman of Microbiology and Immunology, JMC, identified and characterized FHIT. The investigators found that the FHIT gene is located in the human genome's most fragile area. The area is likely to have DNA gaps, breaks and rearrangements when exposed to certain chemicals, including carcinogens. Ever since, they have been working to find out if FHIT's fragility is involved in the start or progression of cancers.

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