Genetic and Phenotypic Characterization of Tumor Cells Derived from Malignant Peripheral Nerve Sheath Tumors of Neurofibromatosis Type 1 Patients

Neurofibromatosis type 1 (NF1) patients have an 8-13% lifetime risk of developing malignant peripheral nerve sheath tumors (MPNST) which have a very poor prognosis. In this study, cells from eight MPNSTs (six primary and two recurrences) of six clinically and genetically well-characterized NF1 patients were taken into culture. Tracing of loss of heterozygosity (LOH) of the NF1, p53, and p16 gene regions or of abnormal karyotypes enabled identification of tumor cells from five MPNSTs. In two other MPNST-derived cell cultures, LOH of the relevant regions in the original tumors could not be detected, indicating that the obtained cells were nonneoplastic cells. Cells from most MPNSTs grew only under standard culture conditions but not under conditions optimized for Schwann cells. These cells were S100-negative and did not exhibit spindle shape which is a characteristic of Schwann cells. Drastically increased proliferation rates were found for most of the MPNST cells in comparison to Schwann cells derived from benign neurofibromas. Our study demonstrates that genetic analysis is effective and essential for verification of MPNST tumor cells in culture. These verified MPNST cells are valuable for further investigations of the biology and pathogenesis of this malignancy as well as for in vitro pharmacologic studies essential for the development of new therapies.