Novel Uveal Melanoma Patient-Derived Organoid Models Recapitulate Human Disease to Support Translational Research.

Autor:	Dalvin LA; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States.; Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota, United States.; School of Medicine, Deakin University, Geelong, Victoria, Australia.; Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong, Victoria, Australia., Andrews-Pfannkoch CM; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States., Miley DR; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States., Hogenson TL; Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota, United States., Erickson SA; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States., Malpotra S; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States., Anderson KJ; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States., Omer ME; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States., Almada LL; Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota, United States., Zhang C; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, United States., Li H; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, United States., Salomao DR; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States., Shields CL; Wills Eye Hospital, Philadelphia, Pennsylvania, United States., Lally SE; Wills Eye Hospital, Philadelphia, Pennsylvania, United States., Malsch RM; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States., Armitage JA; School of Medicine, Deakin University, Geelong, Victoria, Australia.; Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong, Victoria, Australia., Holmes HL; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, United States., Romero MF; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, United States., Fautsch MP; Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States., Markovic SN; Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota, United States.; Department of Immunology, Mayo Clinic, Rochester, Minnesota, United States., Fernandez-Zapico ME; Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota, United States.
Jazyk:	angličtina
Zdroj:	Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2024 Nov 04; Vol. 65 (13), pp. 60.
DOI:	10.1167/iovs.65.13.60
Abstrakt:	Purpose: A lack of representative human disease models has limited the translation of new and more effective treatments in uveal melanoma (UM), the most common primary adult intraocular malignancy. To fill this critical need, we developed and characterized a multicenter biobank of UM patient-derived organoids (PDOs). Methods: UM patients requiring enucleation from 2019 to 2024 donated tumor tissue for PDO generation. PDOs were cultured in Cultrex and compared to donor primary tumor using exome sequencing, RNA sequencing, and immunohistochemistry. The ability of PDOs to maintain the transformed phenotype was evaluated in an orthotopic xenograft model and monitored with fundus imaging. ATAC sequencing and drug response assays were done in a subset of PDOs to explore the feasibility of their use for mechanistic and translational studies. Results: PDOs were successfully established in 40 of 44 cases (91%), retained clinically relevant mutations and molecular markers from the primary tumor, and displayed similar gene expression profiles and well-validated clinical prognostic markers of the disease. PDOs retained tumorigenic capacity in an in vivo model resembling human disease progression. Finally, we demonstrated that PDOs were a feasible platform to identify and evaluate novel therapeutic targets and investigate differential, personalized drug response. Conclusions: PDO models offer a new platform with improved representation of human UM to aid in translational research for this dismal condition.
Databáze:	MEDLINE
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