Available genetically defined cancer models are limited in genotypic and phenotypic complexity and underrepresent the heterogeneity of human cancer. Here, we describe a combinatorial genetic strategy applied to an organoid transformation assay to rapidly generate diverse, clinically relevant bladder and prostate cancer models. Importantly, the clonal architecture of the resultant tumors can be resolved using single-cell or spatially resolved next-generation sequencing to uncover polygenic drivers of cancer phenotypes.
Nature genetics. 2024 Feb 29 [Epub ahead of print]
Shan Li, Alicia Wong, Huiyun Sun, Vipul Bhatia, Gerardo Javier, Sujata Jana, Qian Wu, Robert B Montgomery, Jonathan L Wright, Hung-Ming Lam, Andrew C Hsieh, Bishoy M Faltas, Michael C Haffner, John K Lee
Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Division of Medical Oncology, University of Washington School of Medicine, Seattle, WA, USA., Department of Urology, University of Washington School of Medicine, Seattle, WA, USA., Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. .