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[Preprint]. 2023 Apr 14:2023.04.12.536652. [Version 1] doi: 10.1101/2023.04.12.536652

Combinatorial genetic strategy accelerates the discovery of cancer genotype-phenotype associations

Shan Li, Alicia Wong, Huiyun Sun, Vipul Bhatia, Gerardo Javier, Sujata Jana, Robert B Montgomery, Jonathan L Wright, Hung-Ming Lam, Andrew C Hsieh, Bishoy M Faltas, Michael C Haffner, John K Lee
PMCID: PMC10441433  PMID: 37609344

Abstract

Available genetically-defined cancer models are limited in genotypic and phenotypic complexity and underrepresent the heterogeneity of human cancer. Herein, 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.

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