NF1 and benign neoplasm: Although LOH in NF1 was observed in MPNSTs with high frequency (>four-fold) compared to benign neurofibromas, loss of NF1 is not the sole cause of the malignant progression of benign tumors to MPNSTs in patients with NF1 [31]; several studies have suggested that additional epigenetic or genetic alterations are involved in malignant transformation and tumorigenesis in NF1 [32].