Recent advances in neurofibromatosis type 1.
OBJECTIVE
The past decade, since the identification of the neurofibromatosis type 1 (NF1) gene, has witnessed great advances in our understanding of the role of the NF1 gene in the molecular pathogenesis of NF1-associated clinical abnormalities. The purpose of this review is to highlight recent advances in defining the molecular etiology of nervous system tumors and learning disabilities.


RESULTS
Neurofibromas and optic pathway gliomas result from NF1 inactivation in Schwann cells and astrocytes, respectively, but other cellular factors contribute to tumorigenesis. In addition, malignant progression of plexiform neurofibromas to malignant peripheral nerve sheath tumors requires additional genetic changes, including increased expression of growth factor receptors, molecules that are involved in tumor invasion and metastasis, and inactivation of critical cell cycle regulators. In addition, specific types of NF1 gene mutation may be associated with an increased risk for malignancy in individuals with NF1.


CONCLUSIONS
Research over the past few years has resulted in a detailed understanding of the molecular genetics of benign and malignant tumors affecting individuals with NF1 as well as the development of refined small animal models for these tumors. In addition, clinical studies have begun to define specific subpopulations of patients at risk for cancer and have identified targeted therapies for NF1-associated tumors, based on basic science research advances.
Arun
Deepa
D
Department of Neurology, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, Missouri, USA.
Gutmann
David H
DH
D000328:Adult; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D016514:Genes, Neurofibromatosis 1 / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007859:Learning Disabilities / Q000235:genetics*; D018317:Nerve Sheath Neoplasms / Q000235:genetics; D009423:Nervous System Neoplasms / Q000235:genetics*; D018318:Neurofibroma, Plexiform / Q000235:genetics; D009456:Neurofibromatosis 1 / Q000235:genetics*; D020339:Optic Nerve Glioma / Q000235:genetics; D010524:Peripheral Nervous System Neoplasms / Q000235:genetics