title: HDAC10 as a potential therapeutic target in ovarian cancer.
abstract: We analyzed histone deacetylase 10 (HDAC10) for function in the context of the DNA damage response in BRCA1-null ovarian cancer cells as well as evaluated the potential of general HDAC inhibitors in primary ovarian carcinoma cells. HDAC10 had previously been shown to be highly stimulatory to the process of homology directed repair in HeLa cells, and in this study we investigated whether HDAC10 could impact in vitro the response to anticancer therapies. We hypothesized that the loss of HDAC10 would sensitize cells to platinum therapy.
  
  
  
  We combined informatics analysis of large DNA sequencing datasets from ovarian cancer tumors with tissue culture based assays of primary and established cell lines to test for sensitivity to platinum therapy if HDAC10 activity was inhibited or depleted.
  
  
  
  Using The Cancer Genome Atlas (TCGA) dataset, we found that deep deletions in HDAC10 occurred in 5-10% of ovarian cancer tumors. From the TCGA data we found that low HDAC10 mRNA levels correlated with platinum sensitivity of the tumors. Cell proliferation and DNA damage assays in a BRCA1-null ovarian carcinoma cell line demonstrated reduced DNA repair capacity and sensitization of platinum therapy. Similarly, primary ovarian carcinoma cells demonstrated a sensitization to platinum therapies when treated with HDAC inhibitors.
  
  
  
  From the results of this study, we suggest that the inhibition of HDAC10 may potentiate the effects of platinum therapies in ovarian tumors.
authors.affiliation: Department of Biomedical Informatics, The Ohio State University Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, United States.
authors.forename: Muhtadi M
authors.initials: MM
authors.lastname: Islam
authors.affiliation: Department of Biomedical Informatics, The Ohio State University Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, United States.
authors.forename: Tapahsama
authors.initials: T
authors.lastname: Banerjee
authors.affiliation: Department of Biomedical Informatics, The Ohio State University Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, United States.
authors.forename: Colin Z
authors.initials: CZ
authors.lastname: Packard
authors.affiliation: Department of Biomedical Informatics, The Ohio State University Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, United States.
authors.forename: Shweta
authors.initials: S
authors.lastname: Kotian
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, United States.
authors.forename: Karuppaiyah
authors.initials: K
authors.lastname: Selvendiran
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, United States.
authors.forename: David E
authors.initials: DE
authors.lastname: Cohn
authors.affiliation: Department of Biomedical Informatics, The Ohio State University Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, United States. Electronic address: Jeffrey.Parvin@osumc.edu.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Parvin
mesh_terms: D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D059767:Recombinational DNA Repair / Q000187:drug effects
chemical_list: D056572:Histone Deacetylase Inhibitors; D012333:RNA, Messenger; C447828:HDAC10 protein, human; D006655:Histone Deacetylases; D002945:Cisplatin
keywords: Cisplatin; DNA repair; HDAC10; Ovarian cancer