{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nesic K"],"funding":["Victorian Cancer Agency","U.S. Army Medical Research and Materiel Command","NHMRC","NCI NIH HHS","National Health and Medical Research Council","NIH","NIGMS NIH HHS"],"pagination":["4709-4722"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12593227"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["81(18)"],"pubmed_abstract":["In high-grade serous ovarian carcinoma (HGSC), deleterious mutations in DNA repair gene <i>RAD51C</i> are established drivers of defective homologous recombination and are emerging biomarkers of PARP inhibitor (PARPi) sensitivity. <i>RAD51C</i> promoter methylation (me<i>RAD51C</i>) is detected at similar frequencies to mutations, yet its effects on PARPi responses remain unresolved.In this study, three HGSC patient-derived xenograft (PDX) models with methylation at most or all examined CpG sites in the <i>RAD51C</i> promoter show responses to PARPi. Both complete and heterogeneous methylation patterns were associated with <i>RAD51C</i> gene silencing and homologous recombination deficiency (HRD). PDX models lost me<i>RAD51C</i> following treatment with PARPi rucaparib or niraparib, where "],"journal":["Cancer research"],"pubmed_title":["Acquired &lt;i&gt;RAD51C&lt;/i&gt; Promoter Methylation Loss Causes PARP Inhibitor Resistance in High-Grade Serous Ovarian Carcinoma."],"pmcid":["PMC12593227"],"funding_grant_id":["T32 GM072474","ID400281","P50 CA083636","2P50CA083636","ID400413","F30 CA213737","1062702","P50 CA136393","ID199600","ECRF19003","CRF10–20","DAMD17-01-1-0729","CRF16014","APP1139071"],"pubmed_authors":["Waddell N","Traficante N","Nesic K","Radke M","McNally O","Olesen I","Chai ZQ","Nones K","Harrell MI","Bowtell DDL","Australian Ovarian Cancer Study","Lieschke E","Dall G","Shield-Artin K","Kaufmann SH","Dobrovic A","Vandenberg CJ","Kee D","Wakefield MJ","Musafer A","Hurley RM","McGehee CD","Ho GY","DeFazio A","Swisher EM","Bound N","Scott CL","Kondrashova O","Ghamsari MRE","Weroha SJ"],"additional_accession":[]},"is_claimable":false,"name":"Acquired &lt;i&gt;RAD51C&lt;/i&gt; Promoter Methylation Loss Causes PARP Inhibitor Resistance in High-Grade Serous Ovarian Carcinoma.","description":"In high-grade serous ovarian carcinoma (HGSC), deleterious mutations in DNA repair gene <i>RAD51C</i> are established drivers of defective homologous recombination and are emerging biomarkers of PARP inhibitor (PARPi) sensitivity. <i>RAD51C</i> promoter methylation (me<i>RAD51C</i>) is detected at similar frequencies to mutations, yet its effects on PARPi responses remain unresolved.In this study, three HGSC patient-derived xenograft (PDX) models with methylation at most or all examined CpG sites in the <i>RAD51C</i> promoter show responses to PARPi. Both complete and heterogeneous methylation patterns were associated with <i>RAD51C</i> gene silencing and homologous recombination deficiency (HRD). PDX models lost me<i>RAD51C</i> following treatment with PARPi rucaparib or niraparib, where ","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Sep","modification":"2026-06-05T13:46:56.276Z","creation":"2026-06-05T03:07:03.133Z"},"accession":"S-EPMC12593227","cross_references":{"pubmed":["34321239"],"doi":["10.1158/0008-5472.CAN-21-0774","10.1158/0008-5472.can-21-0774"]}}