A platform for rapid patient-derived cutaneous neurofibroma organoid establishment and screening

Huyen Thi Lam Nguyen; Emily Kohl; Jessica Bade; Stefan E Eng; Anela Tosevska; Ahmad Al Shihabi; Peyton J Tebon; Jenny J Hong; Sarah Dry; Paul C Boutros; Andre Panossian; Sara J C Gosline; Alice Soragni

doi:10.1016/j.crmeth.2024.100772

A platform for rapid patient-derived cutaneous neurofibroma organoid establishment and screening

Cell Rep Methods. 2024 May 20;4(5):100772. doi: 10.1016/j.crmeth.2024.100772. Epub 2024 May 13.

Authors

Affiliations

¹ Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
² Pacific Northwest National Laboratories, Seattle, WA, USA.
³ Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
⁴ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
⁵ Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Division of Hematology-Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁷ Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
⁸ Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA.
⁹ Andre Panossian MD, Plastic Surgery, Pasadena, CA, USA.
¹⁰ Pacific Northwest National Laboratories, Seattle, WA, USA; Department of Biomedical Engineering, Oregon Health and Sciences University, Portland, OR, USA. Electronic address: [email protected].
¹¹ Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: [email protected].

Abstract

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.

Keywords: CP: Cancer biology; CP: Stem cell; HTS screening; benign tumor; cNF tumor organoids; cutaneous neurofibroma; neurofibroma; neurofibromatosis type 1; organoids.

MeSH terms

Humans
Neurofibroma* / pathology
Neurofibroma* / surgery
Neurofibromatosis 1 / pathology
Organoids* / pathology
Skin Neoplasms* / pathology