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Hopkins scientists uncover role of Fanconi's Anemia genes in pancreatic cancer

Scientists at the Johns Hopkins Kimmel Cancer Center have identified three genes, long linked to a rare inherited disease known as Fanconi's Anemia (FA), that now appear to play a role in many cases of pancreatic cancer.

All of the genes identified, when functioning normally, are part of the DNA repair process. The work is reported in the May 15, 2003 issue of Cancer Research.

"What we think we have is a new genetic cause of some cases, approximately 10 percent or more, of pancreatic cancers, one of the most lethal forms of cancer," according to Scott Kern, M.D., professor of oncology and pathology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and director of the study. The good news is that these genes offer new targets for improved treatment, he says.

The genes have all been associated with Fanconi's Anemia. Those affected are born with only a single normal copy of one or more of the genes. Though they do not develop FA, these people often develop pancreatic cancer, usually in their 40s and 50s, about a decade earlier than average age of onset, according to Kern.

"The up side is that while these gene mutations cause a horrific disease, they may actually be the Achilles heel of the tumor and make these particular cancers more responsive to treatment," says Kern.

The culprit genes, including BRCA2, linked by other earlier studies to breast cancer, as well as two other genes FANCC and FANCG, appear to make pancreatic cancer cells highly susceptible to treatment with two FDA-approved cancer drugs mitomycin C and cisplatin. Human clinical trials are now being planned.

Normally, the genes are responsible for keeping DNA in good repair. As DNA is copied for cell replication, these genes compare the copies of DNA and fix any breaks. Mitomycin C and cisplatin work by causing the exact breaks these genes are supposed to repair. In the subset of patients whose pancreatic cancer is cause
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Contact: Valerie Matthews Mehl
mehlva@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
14-May-2003


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