A potential role for NF1 mRNA editing in the pathogenesis of NF1 tumors

摘要: Neurofibromatosis type I (NF1) is a common disorder that predisposes to neoplasia in tissues derived from the embryonic neural crest. The NF1 gene encodes tumor suppressor most likely acts through interaction of its GTPase-activating protein (GAP)-related domain (GRD) with product ras protooncogene. We have previously identified site mRNA, within first half GRD, which undergoes base-modification editing. Editing at changes C U, thereby introducing an in-frame stop codon. RNA editing has been detected all cell types studied, date. In order investigate role played by tumorigenesis, we analyzed 19 and 4 non-NF1 tumors. observed varying levels mRNA different tumors, higher range more malignant tumors (e.g., neurofibrosarcomas) compared benign (cutaneous neurofibromas). Plexiform neurofibromas intermediate also nontumor several individuals, determine extent variability present constitutional whether are varied slightly but were consistent individuals. every case, there was greater level than tissue same patient. These results suggest inappropriately high does play tumorigenesis may result functional equivalent biallelic inactivation suppressor.