Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited disease, affecting 1:3500 individuals worldwide. Nearly all (>90%) of NF1 patients develop plexiform and/or dermal neurofibromas composed of axons, Schwann cells, fibroblasts, perineurial cells, endothelial cells, and mast cells. Schwann cells are believed to be the primary pathogenic cells in neurofibromas because they show biallelic mutation at NF1. However, other cell types present in tumors, in the NF1+/- state, also show cell autonomous defects and have been proposed to be essential for neurofibroma formation. The Cancer Biology program, led by Dr. Nancy Ratner, discovered that the timing the NF1 gene mutation determines whether neurofibroma tumors will form (Cancer Cell, Feb. 2009). In this study, Ratner and her colleagues reported that if the NF1 gene mutated on day 12.5 of a mouse’s embryonic development, neurofibroma tumors formed. If the gene mutated at other times during development, in cell culture studies, cells did not alter proliferation. The new data support a key mechanism in tumor development, in which loss of Nf1 at the correct time in development facilitates tumor formation in a wild-type environment. The discovery was made using the first successful robust neurofibromatosis 1 mouse neurofibroma model, a mouse that Ratner’s team genetically altered to mimic the disease that occurs in humans. Riding on the success of this work, the "Cincinnati Center for Neurofibromatosis Research" was formed with Dr. Ratner as the Principal Investigator. The center will receive funding of one million dollars per year from the National Institutes of Health. Its goal is to identify and therapeutically target signaling pathways that underlie peripheral nerve tumors resulting from NF1 loss of function. The center combines the cutting edge basic science with the ongoing CCHMC pre-clinical therapeutics testing effort funded by the Children’s Tumor Foundation, which is under the supervision of Dr. Tim Cripe.
