Publications

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

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

Nature Genetics Feb 2024

Abstract

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.

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Area

Solid Tumor

Institution Type

Academia

Indication / Modality

Other

Goal of Study

Disease Modeling

Key Genes

TP53, PIK3CA

PAD Project

Analytes Assessed

Extracellular Protein, SNV

Species

Mouse

Panel Used

Custom

Proof Point Demonstrated

Co-occurrence, Clonality

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