New insights into the neurofibroma tumor cells of origin
New insights into the neurofibroma tumor cells of origin
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DOI：
10.1093/noajnl/vdz044
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发表时间：
2020-07-01
期刊：
影响因子：
--
通讯作者：
Le, Lu Q.
中科院分区：
文献类型：
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作者：
Li, Stephen;Chen, Zhiguo;Le, Lu Q.
I型神经纤维瘤病(NF1)是一种使人衰弱的遗传性肿瘤综合征，大约每3000人中就有1人患病。目前存在多种肿瘤的患者是由肿瘤抑制因子神经纤维蛋白(NF1)的双等位基因缺失引起的，NF1是RAS信号的负调控因子。虽然大多数NF1病例的肿瘤形成机制相似，但肿瘤的临床谱系可能会因发育过程中神经脊来源的细胞中NF1杂合性的时空丢失而有所不同。与NF1同名的标志性病变是神经纤维瘤，它是由神经和纤维组织组成的良性雪旺细胞瘤。神经纤维瘤可见于皮肤(皮肤神经纤维瘤)或身体更深层的神经丛附近(丛状神经纤维瘤)。虽然神经纤维瘤多年来一直被认为是雪旺细胞瘤，但确切的时间和起始细胞仍然难以捉摸。这导致了为NF1开发动物模型和成功的治疗方法的困难。最近的遗传学研究的高潮终于开始阐明神经纤维瘤病的详细细胞起源。在这篇综述中，我们将通过一个历史的镜头来检查寻找神经纤维瘤起源的肿瘤细胞，详细描述用于描绘丛状和皮肤神经纤维瘤来源的遗传系统。通过这些新的发现，我们可以更好地理解肿瘤启动过程中的细胞、时间和发育背景。通过利用这些数据，我们希望发现新的治疗靶点和机制来治疗NF1患者。
Neurofibromatosis type I (NF1) is a debilitating inherited tumor syndrome affecting around 1 in 3000 people. Patients present with a variety of tumors caused by biallelic loss of the tumor suppressor neurofibromin (NF1), a negative regulator of Ras signaling. While the mechanism of tumor formation is similar in the majority of NF1 cases, the clinical spectrum of tumors can vary depending on spatiotemporal loss of heterozygosity of NF1 in cells derived from the neural crest during development. The hallmark lesions that give NF1 its namesake are neurofibromas, which are benign Schwann cell tumors composed of nervous and fibrous tissue. Neurofibromas can be found in the skin (cutaneous neurofibroma) or deeper in body near nerve plexuses (plexiform neurofibroma). While neurofibromas have been known to be Schwann cell tumors for many years, the exact timing and initiating cell has remained elusive. This has led to difficulties in developing animal models and successful therapies for NF1. A culmination of recent genetic studies has finally begun to shed light on the detailed cellular origins of neurofibromatosis. In this review, we will examine the hunt for neurofibroma tumor cells of origin through a historical lens, detailing the genetic systems used to delineate the source of plexiform and cutaneous neurofibromas. Through these novel findings, we can better understand the cellular, temporal, and developmental context during tumor initiation. By leveraging this data, we hope to uncover new therapeutic targets and mechanisms to treat NF1 patients.