Method Profile

HDAC Inhibitor Response and Histone Profiling in Uveal Melanoma ALI Organoids

Compare matched tumor and organoid histone features and measure quisinostat-associated viability, RNA and acetylation changes.

Tumor ModelsOrganoids
Quisinostat-associated changes in organoid viability, gene expression and histone modifications.
Quisinostat-associated changes in organoid viability, gene expression and histone modifications. (Leticia Ussem, Karin U. Loeffler, Verena Tischler et al., CC BY 4.0)

Research Applications

Ex vivo evaluation of epigenetic pharmacology and patient-specific model fidelity in uveal melanoma.

Model & Design

ALI organoids established from five patients; histone and drug experiments used their stated subsets.

Experimental Format

Matched tumor–organoid comparisons plus quisinostat, medium and DMSO conditions.

Model Components

  • Component

    Source tissue

    Description

    Fresh or cryopreserved surgically resected uveal melanoma.

  • Component

    Pharmacology

    Description

    Quisinostat at 100 nM and 200 nM for 72 hours, with matched medium/DMSO controls.

Measurements & Endpoints

  • ATP-associated viability luminescence
  • Differential gene expression
  • Mass-spectrometry histone H3/H4 modifications
  • Tumor morphology and molecular features

Analysis

Keep the five-patient establishment cohort, four matched histone pairs and two-tumor/eight-sample RNA drug experiment separate.

Published Evidence

  • Study Design

    Matched tissue characterization combined with HDAC inhibitor treatment.

    Study Sample

    Five source patients; four matched tumor–organoid histone comparisons; two tumors/eight organoid samples for drug RNA profiling.

    Comparison

    Matched source tumor tissue and medium/DMSO treatment controls.

    Finding

    Quisinostat increased several H3/H4 acetylation marks and changed gene expression; viability varied, while bright-field morphology showed little difference.

    Interpretation & Limits
    • Model establishment, molecular profiling and viability measurements used different subsets.
    • The cultures had limited expansion and lacked detectable immune/vascular components.

Sources

  1. Establishment of Uveal Melanoma Patient-Derived Organoids Using an Air-Liquid Interface System for Translational Research ↗