Genomic and Epigenomic Characterization of Tumor Organoid Models

SIMPLE SUMMARY: The patient-derived organoid (PDO) model is a versatile and dynamic tool for investigating individual genomic and epigenomic properties of cancer. PDOs preserve key (epi-)genomic features and maintain physiological and pathological characteristics, resembling patient tumor specimens. Coupled with the next-generation sequencing technology, PDOs can be used to accurately map (epi-)genomic alterations of “living” cancer specimens. Additionally, organoid modeling of matched normal and malignant tissues from the same patient serves as an adequate and valid platform to interrogate cancer-specific features. Because of these advantages, research on PDOs is rapidly growing for the investigation of genotype–phenotype association and precision oncology. ABSTRACT: Tumor organoid modeling has been recognized as a state-of-the-art system for in vitro research on cancer biology and precision oncology. Organoid culture technologies offer distinctive advantages, including faithful maintenance of physiological and pathological characteristics of human disease, self-organization into three-dimensional multicellular structures, and preservation of genomic and epigenomic landscapes of the originating tumor. These features effectively position organoid modeling between traditional cell line cultures in two dimensions and in vivo animal models as a valid, versatile, and robust system for cancer research. Here, we review recent advances in genomic and epigenomic characterization of tumor organoids and the novel findings obtained, highlight significant progressions achieved in organoid modeling of gene–drug interactions and genotype–phenotype associations, and offer perspectives on future opportunities for organoid modeling in basic and clinical cancer research.