Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Pacific Northwest National Laboratories, Seattle, WA, USA.
Cell Rep Methods. 2024 May 20;4(5):100772. doi: 10.1016/j.crmeth.2024.100772. Epub 2024 May 13.
Localized cutaneous neurofibromas (cNFs) are benign tumors that arise in the dermis of patients affected by neurofibromatosis type 1 syndrome. cNFs are benign lesions: they do not undergo malignant transformation or metastasize. Nevertheless, they can cover a significant proportion of the body, with some individuals developing hundreds to thousands of lesions. cNFs can cause pain, itching, and disfigurement resulting in substantial socio-emotional repercussions. Currently, surgery and laser desiccation are the sole treatment options but may result in scarring and potential regrowth from incomplete removal. To identify effective systemic therapies, we introduce an approach to establish and screen cNF organoids. We optimized conditions to support the ex vivo growth of genomically diverse cNFs. Patient-derived cNF organoids closely recapitulate cellular and molecular features of parental tumors as measured by immunohistopathology, methylation, RNA sequencing, and flow cytometry. Our cNF organoid platform enables rapid screening of hundreds of compounds in a patient- and tumor-specific manner.
局限性皮肤神经纤维瘤（cNFs）是一种良性肿瘤，发生于 1 型神经纤维瘤病综合征患者的真皮中。cNFs 是良性病变：它们不会发生恶性转化或转移。然而，它们可能会覆盖身体的很大一部分，有些患者会出现数百到数千个病变。cNFs 会引起疼痛、瘙痒和畸形，从而导致严重的社会情感影响。目前，手术和激光干燥是唯一的治疗选择，但可能会导致疤痕和潜在的不完全切除后复发。为了确定有效的全身治疗方法，我们引入了一种建立和筛选 cNF 类器官的方法。我们优化了条件，以支持基因组多样化的 cNF 的体外生长。患者来源的 cNF 类器官通过免疫组织病理学、甲基化、RNA 测序和流式细胞术测量，紧密重现了亲本肿瘤的细胞和分子特征。我们的 cNF 类器官平台能够以患者和肿瘤特异性的方式快速筛选数百种化合物。
