This is a preprint.
Combinatorial genetic strategy accelerates the discovery of cancer genotype-phenotype associations
- PMID: 37609344
- PMCID: PMC10441433
- DOI: 10.1101/2023.04.12.536652
Combinatorial genetic strategy accelerates the discovery of cancer genotype-phenotype associations
Update in
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A combinatorial genetic strategy for exploring complex genotype-phenotype associations in cancer.Nat Genet. 2024 Mar;56(3):371-376. doi: 10.1038/s41588-024-01674-1. Epub 2024 Feb 29. Nat Genet. 2024. PMID: 38424461 Free PMC article.
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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