Von Recklinghausen neurofibromatosis (NF1) is the most common hereditary syndrome predisposing to neoplasia. NF1 is an autosomal dominant disease caused by a single gene which maps to chromosome 17q11.2. The most common symptomatic manifestation of NF1 is the benign neurofibroma. Our previous studies of tumors in NF1, studies which detected a loss of heterozygosity for DNA markers from the NF1 region of chromosome 17 in malignant tumors, did not detect a loss in neurofibromas. We report here that a more extensive study, including the analysis of neurofibromas from 19 unrelated NF1 patients by using seven probes, failed to detect a single instance of loss of heterozygosity. This finding suggests that neurofibromas are either polyclonal or monoclonal in origin but arise by a mechanism different from that of NF1 malignancies. In order to investigate the first possibility, we analyzed neurofibromas from female NF1 patients by using an X chromosome-specific probe, from the phosphoglycerokinase (PGK) gene, which detects an RFLP. The detected alleles carry additional recognition sites for the methylation-sensitive enzyme HpaII, so that the allele derived from the active X chromosome is digested by HpaII while the one from the hypermethylated, inactive X chromosome is not. We analyzed neurofibromas from 30 unrelated females with NF1. Eight patients were heterozygous for the PGK RFLP. By this assay, neurofibromas from all eight appeared monoclonal in origin. These results suggest that benign neurofibromas in NF1 arise by a mechanism that is different from that of malignant tumors. This mechanism may involve (a) an NF1 gene mutation that, by our analysis, is not detectable as a loss of heterozygosity or (b) a gene or genes other than the NF1 gene.

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ISSN:0002-9297 Note: imported from RIT’s Digital Media Library running on DSpace to RIT Scholar Works in February 2014.

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Department, Program, or Center

Thomas H. Gosnell School of Life Sciences (COS)


RIT – Main Campus