title: Roles of deletion of Arid1a, a tumor suppressor, in mouse ovarian tumorigenesis.
abstract: The chromatin remodeling gene, ARID1A, has been implied as a tumor suppressor, and its somatic inactivating mutations occur in a wide variety of human cancers, most frequently in ovarian and uterine endometrioid and ovarian clear cell carcinomas. Tumors with ARID1A mutations also frequently harbor PTEN or PIK3CA mutations, suggesting their collaboration in tumorigenesis. Here, we used a conditional knockout mouse model in which Arid1a and Pten were deleted either individually or in combination in the mouse ovarian surface epithelium. After 6 months, 59.1% of mice with Arid1a and Pten double knockout developed ovarian endometrioid or undifferentiated carcinoma, whereas the remaining mice showed hyperplasia of ovarian surface epithelium. In contrast, 52 mice with homozygous or heterozygous deletion in either Arid1a or Pten did not develop ovarian lesions. These results demonstrate that inactivation of Arid1a alone is insufficient for tumor initiation but it requires additional genetic alteration(s) such as Pten deletion to drive tumorigenesis.
authors.affiliation: Affiliations of authors: Department of Pathology, Departments of Gynecology and Obstetrics and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD (BG, YSR, RCW, YW, TLW, IMS); Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan (RCW); Department of Surgery, University of Michigan, Ann Arbor, MI (ZW); Genetics Endocrinology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (current address for BG).
authors.forename: Bin
authors.initials: B
authors.lastname: Guan
authors.affiliation: Affiliations of authors: Department of Pathology, Departments of Gynecology and Obstetrics and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD (BG, YSR, RCW, YW, TLW, IMS); Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan (RCW); Department of Surgery, University of Michigan, Ann Arbor, MI (ZW); Genetics Endocrinology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (current address for BG).
authors.forename: Yohan Suryo
authors.initials: YS
authors.lastname: Rahmanto
authors.affiliation: Affiliations of authors: Department of Pathology, Departments of Gynecology and Obstetrics and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD (BG, YSR, RCW, YW, TLW, IMS); Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan (RCW); Department of Surgery, University of Michigan, Ann Arbor, MI (ZW); Genetics Endocrinology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (current address for BG).
authors.forename: Ren-Chin
authors.initials: RC
authors.lastname: Wu
authors.affiliation: Affiliations of authors: Department of Pathology, Departments of Gynecology and Obstetrics and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD (BG, YSR, RCW, YW, TLW, IMS); Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan (RCW); Department of Surgery, University of Michigan, Ann Arbor, MI (ZW); Genetics Endocrinology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (current address for BG).
authors.forename: Yihong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Affiliations of authors: Department of Pathology, Departments of Gynecology and Obstetrics and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD (BG, YSR, RCW, YW, TLW, IMS); Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan (RCW); Department of Surgery, University of Michigan, Ann Arbor, MI (ZW); Genetics Endocrinology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (current address for BG).
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Affiliations of authors: Department of Pathology, Departments of Gynecology and Obstetrics and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD (BG, YSR, RCW, YW, TLW, IMS); Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan (RCW); Department of Surgery, University of Michigan, Ann Arbor, MI (ZW); Genetics Endocrinology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (current address for BG).
authors.forename: Tian-Li
authors.initials: TL
authors.lastname: Wang
authors.affiliation: Affiliations of authors: Department of Pathology, Departments of Gynecology and Obstetrics and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD (BG, YSR, RCW, YW, TLW, IMS); Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan (RCW); Department of Surgery, University of Michigan, Ann Arbor, MI (ZW); Genetics Endocrinology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (current address for BG). ishih@jhmi.edu tlw@jhmi.edu.
authors.forename: Ie-Ming
authors.initials: IeM
authors.lastname: Shih
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics*; D018269:Carcinoma, Endometrioid / Q000235:genetics; D018389:Codon, Nonsense; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D016147:Genes, Tumor Suppressor; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D014157:Transcription Factors
chemical_list: C511511:Arid1a protein, mouse; D014408:Biomarkers, Tumor; D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse