A combinatorial genetic strategy for exploring complex genotype–phenotype associations in cancer

Author:

Li Shan,Wong Alicia,Sun Huiyun,Bhatia Vipul,Javier Gerardo,Jana SujataORCID,Wu Qian,Montgomery Robert B.,Wright Jonathan L.,Lam Hung-Ming,Hsieh Andrew C.ORCID,Faltas Bishoy M.ORCID,Haffner Michael C.,Lee John K.ORCID

Abstract

AbstractAvailable 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.

Funder

U.S. Department of Health & Human Services | NIH | NIH Office of the Director

United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs

Bladder Cancer Advocacy Network

U.S. Department of Health & Human Services | NIH | National Cancer Institute

University of Washington Don L. Rich Urethral Cancer Research Fund Seattle Translational Tumor Research Program in Bladder Cancer

Prostate Cancer Foundation

Seattle Translational Tumor Research Program in Bladder Cancer

Publisher

Springer Science and Business Media LLC

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