title: ARID1A gene mutation in ovarian and endometrial cancers (Review).
abstract: The AT-rich interacting domain‑containing protein 1A gene (ARID1A) encodes ARID1A, a member of the SWI/SNF chromatin remodeling complex. Mutation of ARID1A induces changes in expression of multiple genes (CDKN1A, SMAD3, MLH1 and PIK3IP1) via chromatin remodeling dysfunction, contributes to carcinogenesis, and has been shown to cause transformation of cells in association with the PI3K/AKT pathway. Information on ARID1A has emerged from comprehensive genome‑wide analyses with next‑generation sequencers. ARID1A mutations have been found in various types of cancer and occur at high frequency in endometriosis‑associated ovarian cancer, including clear cell adenocarcinoma and endometrioid adenocarcinoma, and also occur at endometrial cancer especially in endometrioid adenocarcinoma. It has also been suggested that ARID1A mutation occurs at the early stage of canceration from endometriosis to endometriosis‑associated carcinoma in ovarian cancer and also from atypical endometrial hyperplasia to endometrioid adenocarcinoma in endometrial cancer. Therefore, development of a screening method that can detect mutations of ARID1A and activation of the PI3K/AKT pathway might enable early diagnosis of endometriosis‑associated ovarian cancers and endometrial cancers. Important results may also emerge from a current clinical trial examining a multidrug regimen of temsirolimus, a small molecule inhibitor of the PI3K/AKT pathway, for treatment of advanced ovarian clear cell adenocarcinoma with ARID1A mutation and PI3K/AKT pathway activation. Also administration of sorafenib, a multikinase inhibitor, can inhibit cancer proliferation with PIK3CA mutation and resistance to mTOR inhibitors and GSK126, a molecular‑targeted drug can inhibit proliferation of ARID1A‑mutated ovarian clear cell adenocarcinoma cells by targeting and inhibiting EZH2. Further studies are needed to determine the mechanism of chromatin remodeling dysregulation initiated by ARID1A mutation, to develop methods for early diagnosis, to investigate new cancer therapy targeting ARID1A, and to examine the involvement of ARID1A mutations in development, survival and progression of cancer cells.
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160‑8582, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takeda
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160‑8582, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Banno
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160‑8582, Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Okawa
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160‑8582, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Yanokura
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160‑8582, Japan.
authors.forename: Moito
authors.initials: M
authors.lastname: Iijima
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160‑8582, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Irie-Kunitomi
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160‑8582, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160‑8582, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Iida
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160‑8582, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Adachi
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160‑8582, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Umene
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160‑8582, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Nogami
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160‑8582, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Masuda
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160‑8582, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160‑8582, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Tominaga
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160‑8582, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
mesh_terms: D004268:DNA-Binding Proteins; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C112476:ARID1A protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors