Chen Zhiguo, Liu Chiachi, Patel Amish J, Liao Chung-Ping, Wang Yong, Le Lu Q
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA.
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA; Cancer Biology Graduate Program, University of Texas Southwestern Medical Center, Dallas, TX 75390-9133, USA.
Cancer Cell. 2014 Nov 10;26(5):695-706. doi: 10.1016/j.ccell.2014.09.009. Epub 2014 Oct 30.
Neurofibromatosis type 1 is a tumor-predisposing genetic disorder. Plexiform neurofibromas are common NF1 tumors carrying a risk of malignant transformation, which is typically fatal. Little is known about mechanisms mediating initiation and identity of specific cell type that gives rise to neurofibromas. Using cell-lineage tracing, we identify a population of GAP43(+) PLP(+) precursors in embryonic nerve roots as the cells of origin for these tumors and report a non-germline neurofibroma model for preclinical drug screening to identify effective therapies. The identity of the tumor cell of origin and facility for isolation and expansion provides fertile ground for continued analysis to define factors critical for neurofibromagenesis. It also provides unique approaches to develop therapies to prevent neurofibroma formation in NF1 patients.
1型神经纤维瘤病是一种具有肿瘤易感性的遗传性疾病。丛状神经纤维瘤是常见的1型神经纤维瘤病肿瘤，具有恶性转化风险，通常是致命的。关于介导神经纤维瘤起始和特定细胞类型身份的机制知之甚少。通过细胞谱系追踪，我们确定胚胎神经根中一群GAP43(+) PLP(+)前体细胞是这些肿瘤的起源细胞，并报告了一种用于临床前药物筛选以确定有效疗法的非种系神经纤维瘤模型。肿瘤起源细胞的身份以及分离和扩增的便利条件为继续分析以确定神经纤维瘤发生的关键因素提供了丰富的研究基础。它还为开发预防1型神经纤维瘤病患者神经纤维瘤形成的疗法提供了独特的方法。
