{"doi":"10.17615/eq7n-0p73","title":"Coexistent ARID1A–PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling","abstract":"Ovarian clear-cell carcinoma (OCCC) is an aggressive form of ovarian cancer with high ARID1A mutation rates. Here we present a mutant mouse model of OCCC. We find that ARID1A inactivation is not sufficient for tumor formation, but requires concurrent activation of the phosphoinositide 3-kinase catalytic subunit, PIK3CA. Remarkably, the mice develop highly penetrant tumors with OCCC-like histopathology, culminating in hemorrhagic ascites and a median survival period of 7.5 weeks. Therapeutic treatment with the pan-PI3K inhibitor, BKM120, prolongs mouse survival by inhibiting tumor cell growth. Cross-species gene expression comparisons support a role for IL-6 inflammatory cytokine signaling in OCCC pathogenesis. We further show that ARID1A and PIK3CA mutations cooperate to promote tumor growth through sustained IL-6 overproduction. Our findings establish an epistatic relationship between SWI/SNF chromatin remodeling and PI3K pathway mutations in OCCC and demonstrate that these pathways converge on pro-tumorigenic cytokine signaling. We propose that ARID1A protects against inflammation-driven tumorigenesis.","journal":"UNC Libraries","year":2020,"id":141511,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":353517,"name":"Jesse R. Raab","orcid":"0000-0001-6387-8994","position":1,"is_corresponding":false},{"id":275068,"name":"Terry Magnuson","orcid":"0000-0002-0792-835X","position":2,"is_corresponding":false},{"id":277833,"name":"Ronald L. Chandler","orcid":"0000-0001-5775-2594","position":3,"is_corresponding":false},{"id":275088,"name":"Fernando Pardo‐Manuel de Villena","orcid":"0000-0002-5738-5795","position":4,"is_corresponding":false},{"id":541021,"name":"Della Yee","orcid":"0000-0002-2304-9873","position":5,"is_corresponding":false},{"id":407735,"name":"William Y. Kim","orcid":"0000-0001-7922-2156","position":6,"is_corresponding":false},{"id":593785,"name":"Jessie Xiong","orcid":null,"position":7,"is_corresponding":false},{"id":245448,"name":"David B. Darr","orcid":"0000-0002-2843-7648","position":8,"is_corresponding":false},{"id":600560,"name":"Daniel Serber","orcid":null,"position":9,"is_corresponding":false},{"id":229075,"name":"Jonathan C. Schisler","orcid":"0000-0001-7382-2783","position":10,"is_corresponding":false},{"id":52027,"name":"Jeffrey S. Damrauer","orcid":"0000-0001-8148-0285","position":11,"is_corresponding":false},{"id":1916,"name":"Matthew D. Wilkerson","orcid":"0000-0003-2727-0230","position":12,"is_corresponding":false},{"id":438261,"name":"John P. Didion","orcid":"0000-0002-8111-6261","position":13,"is_corresponding":false},{"id":400904,"name":"Joshua Starmer","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:24.429854Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}