SMARCA4 loss increases RNA Polymerase II pausing and elevates R-loops to inhibit BRCA1-mediated repair in ovarian cancer
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X Zhu, Z Fu, G Aceto, J St-Germain, K Liu…
Cancer …, 2025
aacrjournals.org
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare, aggressive cancer affecting young women, driven by inactivating mutations in SMARCA4, a key SWI/SNF chromatin remodeling gene. To uncover its druggable vulnerabilities, we performed a compound screen and found that SCCOHT cells and tumors were sensitive to PARP inhibitors. Paradoxically, SCCOHT displayed BRCA-deficient traits despite retaining wild-type BRCA1 expression. Elevated R-loop in SCCOHT sequestered BRCA1, limiting its …
