The overall objective of this research is to provide a diagnostic test for the identification of individuals at high risk for neurofibromatosis. This neoplasm is an autosomal dominant disorder with a frequency of 1 in 3000 diagnosed on clinical criteria. The disease has a high mutation rate which may be due to failure to recognize the presence of the disease in the parent. Observations of skin fibroblasts (SF) derived from patients genetically susceptible to cancer, i.e., familiar polyposis, indicate increased sensitivity to oncogenic virus transformation, and the applicability of these observations to detect neurofibromatosis risk is suggested. Our pilot retrospective study with SF from individuals with neurofibromatosis clearly suggests such a correlation exists based on relatively high sensitivity to transformation. The proposed work will specifically focus on assessing this transformation assay as a convenient, reliable, and rapid procedure for prenatal identification of these individuals in families with neurofibromatosis; as well as postnatal and prenatal examination. At least 20 families with or without neurofibromatosis will be monitored; personal and family history will be obtained. SF cultures will be established from amniotic fluid cells, and from skin punch biopsies and examined for sensitivity to transformation by standardized doses of Kirsten murine sarcoma virus (KiMSV). The highest dose of KiMSV (50% infective dose/ml) that effects SF transformation will be correlated with the history, and analyzed for association. As the result of this feasibility study, evidence could be presented that high risk pregnancy in terms of neurofibromatosis can be diagnosed prenatally. In view of the important public health goal of cancer prevention, the diagnostic test may also offer a scientific basis for counseling of individuals with neurofibromatosis.