National Center for Advancing Translational Sciences (NCATS), Division of Pre-clinical Innovation, National Institutes of Health, Bethesda, MD, USA.
Sage Bionetworks, Seattle, WA, USA.
Sci Data. 2018 Jun 12;5:180106. doi: 10.1038/sdata.2018.106.
Neurofibromatosis type I (NF1) is an autosomal dominant genetic condition characterized by peripheral nervous system tumors (PNSTs), including plexiform neurofibromas (pNFs) that cause nerve dysfunction, deformity, pain damage to adjacent structures, and can undergo malignant transformation. There are no effective therapies to prevent or treat pNFs. Drug discovery efforts are slowed by the 'benign' nature of the Schwann cells that are the progenitor cells of pNF. In this work we characterize a set of pNF-derived cell lines at the genomic level (via SNP Arrays, RNAseq, and Whole Exome- Sequencing), and carry out dose response-based quantitative high-throughput screening (qHTS) with a collection of 1,912 oncology-focused compounds in a 1536-well microplate cell proliferation assays. Through the characterization and screening of NF1, NF1 and NF1 Schwann cell lines, this resource introduces novel therapeutic avenues for the development for NF1 associated pNF as well as all solid tumors with NF1 somatic mutations. The integrated data sets are openly available for further analysis at http://www.synapse.org/pnfCellCulture.
神经纤维瘤病 1 型（NF1）是一种常染色体显性遗传疾病，其特征为周围神经系统肿瘤（PNSTs），包括引起神经功能障碍、畸形、疼痛损伤邻近结构的丛状神经纤维瘤（pNFs），并可能发生恶性转化。目前尚无有效的治疗方法来预防或治疗 pNFs。由于施万细胞（pNF 的祖细胞）具有“良性”性质，药物发现工作进展缓慢。在这项工作中，我们在基因组水平上对一组 pNF 衍生的细胞系进行了表征（通过 SNP 阵列、RNAseq 和全外显子测序），并在 1536 孔微孔板细胞增殖测定中使用包含 1912 种肿瘤学重点化合物的文库进行基于剂量反应的定量高通量筛选（qHTS）。通过对 NF1、NF1 和 NF1 施万细胞系的表征和筛选，该资源为 NF1 相关 pNF 以及所有具有 NF1 体细胞突变的实体瘤的开发引入了新的治疗途径。整合后的数据集可在 http://www.synapse.org/pnfCellCulture 上进行进一步分析。
