Cell of origin and the contribution of microenvironment in NF1 tumorigenesis and therapeutic implications

The hallmark feature of neurofibromatosis type 1 (NF1) is the development of multiple benign peripheral nerve sheath tumors (PNST), also known as neurofibroma. One of the major clinical consequences of germline NF1 mutations in patients is the conversion of a relatively tumor-resistant organ, the peripheral nerve, to a highly tumor-susceptible organ. However, it is not clear about the molecular and cellular mechanism(s) by which NF1 heterozygous mutations in the germline alter nerve cell biology during development and disrupt nerve microenvironment, thereby promoting tumor development. At least some of the answers to these fundamental questions lie in the identification of the cell(s) of origin of these benign and malignant peripheral nerve sheath tumors. This review summarizes the recent progress of the cell-of-origin research on NF1-associated tumors, which has provided important insights into the design of therapies for preventing and treating these incurable human tumors.