Ratner Nancy, Miller Shyra J
Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.
Nat Rev Cancer. 2015 May;15(5):290-301. doi: 10.1038/nrc3911. Epub 2015 Apr 16.
Neurofibromatosis type 1 (NF1) is a common genetic disorder that predisposes affected individuals to tumours. The NF1 gene encodes a RAS GTPase-activating protein called neurofibromin and is one of several genes that (when mutant) affect RAS-MAPK signalling, causing related diseases collectively known as RASopathies. Several RASopathies, beyond NF1, are cancer predisposition syndromes. Somatic NF1 mutations also occur in 5-10% of human sporadic cancers and may contribute to resistance to therapy. To highlight areas for investigation in RASopathies and sporadic tumours with NF1 mutations, we summarize current knowledge of NF1 disease, the NF1 gene and neurofibromin, neurofibromin signalling pathways and recent developments in NF1 therapeutics.
1型神经纤维瘤病(NF1)是一种常见的遗传性疾病,使受影响的个体易患肿瘤。NF1基因编码一种名为神经纤维瘤蛋白的RAS GTP酶激活蛋白,是几个(发生突变时)影响RAS-MAPK信号传导的基因之一,这些基因导致的相关疾病统称为RAS病。除NF1外,几种RAS病是癌症易感综合征。体细胞NF1突变也发生在5%-10%的人类散发性癌症中,可能导致治疗耐药。为了突出RAS病和具有NF1突变的散发性肿瘤的研究领域,我们总结了目前关于NF1疾病、NF1基因和神经纤维瘤蛋白、神经纤维瘤蛋白信号通路以及NF1治疗学最新进展的知识。