Individuals with neurofibromatosis 1 (NF1) often develop benign neurofibromas, which can progress to aggressive, malignant tumors. Neurofibromatosis Research Program grant recipient Tyler Jacks and his colleagues at the Massachusetts Institute of Technology generated mice with mutated Nf1 and p53 genes, and found that these genes cooperate in the development of malignant NF1 tumors. They focused on the p53 gene since other studies have shown that it is involved in the formation of malignant tumors. In addition, p53 and Nf1 are both located on chromosome 11 in mice suggesting a potential association between these two genes. Dr. Jacks and his colleagues have also developed a mouse model for astrocytoma, which is an aggressive brain tumor found in both NF1 and NF2 patients. They have also generated a mouse model of benign neurofibromas with mice composed in part of cells lacking the Nf1 gene. These mouse models should provide valuable insights into the fundamental aspects of disease development and may be used for testing therapeutic strategies for NF1.
Cichowski K, Shih T, Schmitt E, et al. 1999. Mouse models of tumor development in neurofibromatosis type 1. Science, 286: 2172-2176.
Reilly K, Loisel D, Bronson R, et al. 2000. NF1;Trb53 mutant mice develop glioblastoma with evidence of strain-specific effects. Nature Genetics, 26:109-113.
For additional publications arising from this grant and more information about the NFRP and other DOD-sponsored programs visit https://cdmrp.army.mil.
Neurofibromatosis 1 (NF1), a multisystem genetic disorder, is highly variable among patients of the same age, affected members of a single family, and even within individual patients at different times in their lives. Neurofibromatosis Research Program grant recipient J. M. Friedman and his colleagues at the University of British Columbia have determined that certain clinical features often cluster together in individual patients and within affected families. For example, three types of pigmented lesions (Lisch nodules, intertriginous freckles, and cafi-au-lait spots) were commonly found together in individual NF1 patients. In addition, strong associations between the occurrence of Lisch nodules, cutaneous neurofibromas, subcutaneous neurofibromas, and intertriginous freckling were observed within families affected by NF1. Dr. Friedman and his colleagues are using a combination of clinical, epidemiological, molecular genetic, and statistical methods, in addition to the resources of several large NF databases to complete this study. Overall, this study is helping to define subgroups of NF1 patients who are especially likely to develop serious complications, which may allow screening efforts to be focused on those at the greatest risk. In addition, insight gained on the clinical variability of NF1 may lead to better understanding of how various manifestations of NF1 arise and new approaches to treatment for this disease.
Szudek J, Birch P, Riccardi V, et al. 2000. Associations of clinical features in neurofibromatosis 1 (NF1). Genetic Epidemiology, 19(4):429-39.
Szudek J, Joe H, Friedman JM. Analysis of intra-familial phenotypic correlation in neurofibromatosis 1 (NF1). (submitted for publication)
For additional publications arising from this grant and more information about the NFRP and other DOD-sponsored programs visit https://cdmrp.army.mil