文章：

一种在癌症中常见突变的ras病变基因：1型神经纤维瘤病肿瘤抑制因子

A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor

原文发布日期：2015-04-16

DOI: 10.1038/nrc3911

类型: Review Article

开放获取: 否

要点：

1. The neurofibromatosis type 1 (NF1) research community has identified the NF1 gene and has developed mouse models of plexiform neurofibroma, optic pathway glioma, malignant peripheral nerve sheath tumours and juvenile myelomonocytic leukaemia, all of which are tumours that are found in patients with NF1.
2. The NF1 gene encodes a RAS GTPase-activating protein known as neurofibromin and is one of several genes that (when mutant) affect RAS–MAPK signalling, causing related diseases collectively known as RASopathies.
3. Preclinical and clinical testing consortia have found that inhibition of MEK shrinks benign tumours but that combinatorial therapies are likely to be needed for NF1-related malignancies. These may include targeting of other RAS effector pathways. Treatments that target NF1 could also be tested as treatments for other RASopathies.
4. The neurofibromin protein has been studied, and many potential interacting partners have been identified. However, many questions remain concerning the functional importance of possible interaction partners and roles of neurofibromin protein domains, and the interactions between neurofibromin and cyclic AMP signalling pathways.
5. NF1 mutations are common in most sporadic tumour types and can mediate resistance to therapy.

要点翻译：

1. 1型神经纤维瘤病（NF1）研究领域已成功识别NF1基因，并建立了丛状神经纤维瘤、视路胶质瘤、恶性外周神经鞘瘤及幼年型粒单核细胞白血病的小鼠模型——这些均为NF1患者中常见的肿瘤类型。
2. NF1基因编码一种名为神经纤维瘤蛋白的RAS GTP酶激活蛋白。该基因是多个（发生突变时）影响RAS-MAPK信号通路的基因之一，由此引发的相关疾病统称为RASopathy综合征。
3. 临床前与临床测试联盟发现，抑制MEK可使良性肿瘤缩小，但NF1相关恶性肿瘤可能需要联合治疗方案，其中可能包括靶向其他RAS效应通路。针对NF1的治疗策略也有望应用于其他RASopathy疾病的治疗。
4. 目前已完成对神经纤维瘤蛋白的研究，并鉴定出许多潜在相互作用因子。然而关于这些相互作用因子的功能重要性、神经纤维瘤蛋白各结构域的作用，以及神经纤维瘤蛋白与环磷酸腺苷信号通路的相互作用机制，仍存在诸多未解之谜。
5. NF1突变在多数散发性肿瘤中普遍存在，并可能介导治疗耐药性。

英文摘要：

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.

摘要翻译： 

1型神经纤维瘤病（NF1）是一种常见的遗传性疾病，易使患者发生肿瘤。NF1基因编码一种称为神经纤维瘤蛋白的RAS GTP酶激活蛋白，是多个（突变时）影响RAS-MAPK信号通路的基因之一，可引起统称为RASopathies的相关疾病。除NF1外，多种RASopathies均为癌症易感综合征。体细胞NF1突变也见于5-10%的人类散发性癌症，并可能导致治疗耐药。为明确RASopathies及伴NF1突变的散发性肿瘤的研究方向，我们综述了NF1疾病、NF1基因与神经纤维瘤蛋白、神经纤维瘤蛋白信号通路的现有认识，以及NF1治疗学的最新进展。

原文链接：

A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor