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

Autor:	Nguyen HTL; Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA., Kohl E; Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA., Bade J; Pacific Northwest National Laboratories, Seattle, WA, USA., Eng SE; 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., Tosevska A; Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA., Al Shihabi A; 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., Tebon PJ; Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA., Hong JJ; Division of Hematology-Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA., Dry S; Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA., Boutros PC; 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., Panossian A; Andre Panossian MD, Plastic Surgery, Pasadena, CA, USA., Gosline SJC; Pacific Northwest National Laboratories, Seattle, WA, USA; Department of Biomedical Engineering, Oregon Health and Sciences University, Portland, OR, USA. Electronic address: sara.gosline@pnnl.gov., Soragni A; 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: alices@mednet.ucla.edu.
Jazyk:	angličtina
Zdroj:	Cell reports methods [Cell Rep Methods] 2024 May 20; Vol. 4 (5), pp. 100772. Date of Electronic Publication: 2024 May 13.
DOI:	10.1016/j.crmeth.2024.100772
Abstrakt:	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. Competing Interests: Declaration of interests A.S. and P.C.B. are founders and owners of Icona BioDx. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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