Combinatorial organoid mutagenesis screen reveals gene constellations driving malignant transformation, pathology and chemosensitivity in high-grade serous ovarian carcinoma.

ABSTRACT: High-grade serous ovarian carcinoma (HGSC) is the sixth leading cause of cancer-related death among women. Many cases arise from the Fallopian tubal epithelium (TE), exhibit numerous mutations, and present heterogenous pathological features. However, the contribution of specific mutation combinations to cellular transformation, pathological phenotype and chemotherapeutic response remains poorly understood. Here, we used a Trp53-deficient mouse TE-derived organoid platform to perform combinatorial CRISPR mutagenesis of 20 candidate HGSC driver genes. Mutations in Nf1, Cdkn2a and Map2k4 were most frequently observed in transformed organoids. Upon transplantation into mice, those containing Map2k4 mutations predominantly gave rise to papillary-glandular hist

SUBMITTER: Phuong DJ 

PROVIDER: S-EPMC12248148 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature