TY - JOUR T1 - A rapid platform for 3D patient-derived cutaneous neurofibroma organoid establishment and screening JF - bioRxiv DO - 10.1101/2022.11.07.515469 SP - 2022.11.07.515469 AU - Huyen Thi Lam Nguyen AU - Emily Kohl AU - Jessica Bade AU - Stefan E. Eng AU - Anela Tosevska AU - Ahmad Al Shihabi AU - Jenny J. Hong AU - Sarah Dry AU - Paul C. Boutros AU - Andre Panossian AU - Sara Gosline AU - Alice Soragni Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/11/07/2022.11.07.515469.abstract N2 - Localized cutaneous neurofibromas (cNFs) are benign tumors that arise in the dermis of patients affected by Neurofibromatosis Type 1 syndrome (NF1). cNFs are fundamentally benign lesions: they do not undergo malignant transformation or metastasize. Nevertheless, in NF1 patients, 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 with substantial socio-emotional repercussions. To date, surgical removal or laser desiccation are the only treatment options, but can result in scarring and the leave a potential for regrowth.To support drug discovery efforts focused on identifying effective systemic therapies for cNF, we introduce an approach to routinely establish and screen cNF tumor organoids. We optimized conditions to support ex vivo growth of genomically-diverse cNFs. Patient-derived cNF organoids closely recapitulate the molecular and cellular heterogeneity of these tumors as measured by immunohistopathology, DNA methylation, RNA-seq and flow cytometry. Our tractable patient-derived cNF organoid platform enables rapid screening of hundreds of compounds in a patient- and tumor-specific manner.Competing Interest StatementThe authors have declared no competing interest. ER -