Single-cell analysis of mouse organoid models for preclinical oncology research

The use of genetically engineered model organisms is valuable in advanced preclinical oncology research for disease progression and drug development. Bladder cancer is caused by upwards of 5 mutations or more in the same tumor. Studying diverse higher-order genetic interactions that drive bladder cancer is difficult with current models of tumorigenesis and limited by bulk sequencing, which fails to directly discern clonality and resolve mutational co-occurrence patterns. Dr. John Lee, of Fred Hutchinson Cancer Center, sought to better understand which combinations of mutations were critical by leveraging a mouse model, organoids, and gene-editing approaches. Using single-cell DNA sequencing, a system was developed for investigating the functional impact of higher-order genetic interactions in cancer.