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Genetic breakdown in Fanconi anemia may have link to HPV-associated cancer
Date:12/3/2008

s cell carcinoma of the head, neck, skin or anogenital region. Current treatments for these cancers are limited mainly to surgery or radiation, which is less than ideal because of underlying DNA instability in Fanconi anemia patients. The current study is part of a larger effort to find more effective and safer treatments, said Dr. Wells, also associate professor of pediatrics at the University of Cincinnati College of Medicine.

The FA gene complex and pathway are known to play an important role in DNA repair. According to this study, which used skin cells from Fanconi anemia patients, FA also helps maintain proper functioning of the cell cycle specifically a cell's exit from the duplication of genetic material prior to division.

The current study examined Fanconi anemia-related squamous cell carcinoma with HPV because some research suggests a connection, although molecularly it remains unproven. One reason is the molecular changes that lead to cancer in FA-deficient keratinocytes (the skin cell of origin for squamous cell carcinoma) are poorly understood. This study, which uses keratinocytes, begins to help explain some of these changes.

Together with physicians in the Fanconi Anemia Comprehensive Care Center at Cincinnati Children's, Dr. Wells' team collected keratinocytes from patients. They analyzed the cells in a laboratory cell culture system that recreates the biology of normal epithelial tissue, or skin. Fanconi Anemia patients can be deficient in one of 13 distinct genes, all working in the same pathway. Most patients have what is called the FANCA complementation group, with mutations in the FANCA gene.

The HPV cancer genes E6/E7 were artificially introduced to FANCA-patient skin cells and grown in the three-dimensional organotypic raft culture that simulates skin. The investigators observed irregular cell growth and increased skin thickness in the culture. Restoring FANCA gene function in the skin reduced irregular c
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Contact: Nick Miller
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

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