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technical note

Model organisms and patient-derived xenografts for preclinical oncology research

The use of model organisms and patient-derived xenografts (PDX) are valuable tools 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.


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AML subpopulations defined by SNV, CNV, and protein expression
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Copy number variants (CNV) and single nucleotide variants (SNV) simultaneously detected in single cells
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Single-cell DNA sequencing resolves the genetic complexity underlying CLL progression
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