The research advances of neurofibromatosis type 1 pathogenesis

Neurofibromatosis 1(NF1)is a common genetic condition in which affected individuals are prone to the development of benign and malignant tumors.The NF1 tumor suppressor encodes a protein product neurofibromin,which functions as a negative regulator of RAS.Loss of neurofibromin expression in NF1-associated tumors or NF1-deficient mouse cells is associated with elevated RAS activity and increased cell proliferation.Despite this straightforward pathophysiologic association between RAS activity mediating by neurofibromin and tumorigenesis,recent insights from mouse and Drosophila modeling studies have suggested additional functions for neurofibromin and implicated NF1 heterozygosity in tumor formation.Lastly,NF1 knockout mouse studies have also demonstrated important roles for cooperating genetic changes that accelerate tumorigenesis as well as modifier genes that impact cancer susceptibility.