Critical Role of PTEN for Development and Progression of Nerve Sheath Tumors in Neurofibromatosis Type 1

Abstract

Evaluation of: Gregorian C, Nakashima J, Dry SM et al.: PTEN dosage is essential for neurofibroma development and malignant transformation. Proc. Natl Acad. Sci. USA 106(46), 19479-19484 (2009). Neurofibromatosis type 1 (NF1) is among the most common inherited tumor-predisposing syndromes in humans. Development of malignant peripheral nerve sheath tumors (MPNSTs) from neurofibroma significantly affects the morbidity and mortality of NF1 patients. The authors demonstrate, using different genetically engineered mouse models, that loss of the tumor suppressor Pten in combination with overexpression of the K-ras oncogene is an important step in MPNST development. In both mouse and human tumors, the transition from low-grade neurofibromas to MPNST is associated with reduced Pten expression, deregulated mTOR signaling activity and increased proliferation. This tumor transition can be monitored by (18)F-fluoro-D-glucose-PET, offering close clinical monitoring of NF1 patients and thus early detection of MPNST development in the future.