A Combinatorial Genetic Strategy for Exploring Complex Genotype-phenotype Associations in Cancer

Overview

Journal Nat Genet

Specialty Genetics

Date 2024 Feb 29

PMID 38424461

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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Wu Q, Fu X, Liu G, He X, Li Y, Ou C J Hematol Oncol. 2025; 18(1):12.

PMID: 39881381 PMC: 11780989. DOI: 10.1186/s13045-025-01665-7.

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