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

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

Journal

Cell reports methods
ISSN: 2667-2375
Titre abrégé: Cell Rep Methods
Pays: United States
ID NLM: 9918227360606676

Informations de publication

Date de publication:
07 May 2024
Historique:
received: 06 01 2023
revised: 10 02 2024
accepted: 19 04 2024
medline: 15 5 2024
pubmed: 15 5 2024
entrez: 14 5 2024
Statut: aheadofprint

Résumé

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.

Identifiants

DOI: 10.1016/j.crmeth.2024.100772 PMID: 38744290
pubmed: 38744290
pii: S2667-2375(24)00116-4
doi: 10.1016/j.crmeth.2024.100772
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

100772

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests A.S. and P.C.B. are founders and owners of Icona BioDx.

Auteurs

Huyen Thi Lam Nguyen (HTL)

Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Emily Kohl (E)

Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Jessica Bade (J)

Pacific Northwest National Laboratories, Seattle, WA, USA.

Stefan E 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.

Anela Tosevska (A)

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.

Ahmad 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.

Peyton J Tebon (PJ)

Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Jenny J Hong (JJ)

Division of Hematology-Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Sarah Dry (S)

Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Paul C 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.

Andre Panossian (A)

Andre Panossian MD, Plastic Surgery, Pasadena, CA, USA.

Sara J C 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.

Alice 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.

Classifications MeSH