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Newly Discovered Gene Could Be A Biological Marker for Colorectal Cancer

PHILADELPHIA (November 1, 1999) -- Scientists at Fox Chase Cancer Center have discovered that a gene involved in repairing damaged DNA in cells is mutated in some cancers. A completed study of the novel gene focused on colorectal tumors and could have implications in diagnosing the disease. The finding, made in the Fox Chase lab of Alfonso Bellacosa, M.D., is published in the November journal Nature Genetics.

The gene named Med1 produces a protein that removes the damaged portion of the DNA, allowing the cell to patch the damaged area with new DNA. This DNA repair process is critical for correcting certain types of DNA damage. In many of the tumors studied, Med1 was mutated and unable to perform its job.

The published study conducted at Fox Chase Cancer Center in Philadelphia, the Institute of Medical Genetics of the Catholic University in Rome and the University of Helsinki looked at colorectal, endometrial and pancreatic tumors that exhibited unstable DNA. Med1 was mutated in 25 percent of those tumors. The largest collection of specimens came from nonpolyposis colorectal tumors - the most common form of hereditary colorectal cancer.

"This finding is a critical step in determining what role Med1 has in colorectal cancer," explains Alfonso Bellacosa, M.D., an associate member of Fox Chase Cancer Center. "If in further studies we find that a mutated Med1 allows cancer to develop, it could be a biological marker for a subset of hereditary or sporadic colorectal cancer."

Biological markers are often used as predictors indicating a person's risk of developing cancer. Such markers include PSA (prostate-specific antigen) for prostate cancer and the genes BRCA1 and BRCA2 for breast cancer.

Bellacosa adds, "Using Med1 as a biological marker isn't the only potential for this gene. By studying Med1, we hope to understand some basic properties of DNA repair. It's also possible that Med1 could be used in the lab as a tool to detect DNA damage and study mutations in other genes. It's important to put this into perspective. We are just at the beginning. Much more work needs to be completed on Med1." Med1 was cloned successfully in 1996 when the protein's function was initially discovered.

Joseph R. Testa, Ph.D., recently designated as Director of Fox Chase's Human Genetics Program, states, "Med1 appears to represent a truly novel type of cancer gene, and further investigations on its activities might yield important insights regarding the mechanisms by which DNA repair contributes to the development of some forms of cancer." The identification of new markers such as Med1 may offer the possibility of earlier diagnosis and intervention with more effective, individually tailored therapies.

"We are very pleased to see that this development arose out of Fox Chase's commitment to the development and expansion of its new Human Genetics Program, an important component of the Center's initiative on cancer prevention," says Testa.

Fox Chase Cancer Center is one of 36 National Cancer Institute-designated comprehensive cancer centers in the nation. Fox Chase activities include basic and clinical research; prevention, detection, and treatment of cancer; and community outreach programs.

Fox Chase Cancer Center, part of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence four consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach.  For more information, call 1-888-FOX CHASE or (1-888-369-2427).

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