| Title | A combinatorial genetic strategy for exploring complex genotype-phenotype associations in cancer. |
| Publication Type | Journal Article |
| Year of Publication | 2024 |
| Authors | Li S, Wong A, Sun H, Bhatia V, Javier G, Jana S, Wu Q, Montgomery RB, Wright JL, Lam H-M, Hsieh AC, Faltas BM, Haffner MC, Lee JK |
| Journal | Nat Genet |
| Volume | 56 |
| Issue | 3 |
| Pagination | 371-376 |
| Date Published | 2024 Mar |
| ISSN | 1546-1718 |
| Keywords | Genetic Association Studies, Genotype, Humans, Male, Neoplasms, Phenotype |
| 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. |
| DOI | 10.1038/s41588-024-01674-1 |
| Alternate Journal | Nat Genet |
| PubMed ID | 38424461 |
| PubMed Central ID | PMC10937382 |
| Grant List | R37 CA230617 / CA / NCI NIH HHS / United States DP2 CA271301 / CA / NCI NIH HHS / United States R01 CA276308 / CA / NCI NIH HHS / United States P30 CA015704 / CA / NCI NIH HHS / United States DP2 CA271301 / CA / NCI NIH HHS / United States DP2 CA271301 / CA / NCI NIH HHS / United States P30 CA015704 / CA / NCI NIH HHS / United States R01 CA276308 / CA / NCI NIH HHS / United States R37 CA230617 / CA / NCI NIH HHS / United States |