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Updated: Dec 23, 2025
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Non-coding somatic mutations converge on the PAX8 pathway in ovarian cancer
Rosario I Corona1,2, Ji-Heui Seo3,4, Xianzhi Lin1
1Cedars-Sinai Women's Cancer Program at the Samuel Oschin Cancer Center, Los Angeles, CA, USA.
Abstract:
The functional consequences of somatic non-coding mutations in ovarian cancer (OC) are unknown. To identify regulatory elements (RE) and genes perturbed by acquired non-coding variants, here we establish epigenomic and transcriptomic landscapes of primary OCs using H3K27ac ChIP-seq and RNA-seq, and then integrate these with whole genome sequencing data from 232 OCs. We identify 25 frequently mutated regulatory elements, including an enhancer at 6p22.1 which associates with differential expression of ZSCAN16 (P = 6.6 × 10-4) and ZSCAN12 (P = 0.02). CRISPR/Cas9 knockout of this enhancer induces downregulation of both genes. Globally, there is an enrichment of single nucleotide variants in active binding sites for TEAD4 (P = 6 × 10-11) and its binding partner PAX8 (P = 2×10-10), a known lineage-specific transcription factor in OC. In addition, the collection of cis REs associated with PAX8 comprise the most frequently mutated set of enhancers in OC (P = 0.003). These data indicate that non-coding somatic mutations disrupt the PAX8 transcriptional network during OC development.
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