Open Access

ARID1A gene mutation in ovarian and endometrial cancers (Review)

  • Authors:
    • Takashi Takeda
    • Kouji Banno
    • Ryuichiro Okawa
    • Megumi Yanokura
    • Moito Iijima
    • Haruko Irie‑Kunitomi
    • Kanako Nakamura
    • Miho Iida
    • Masataka Adachi
    • Kiyoko Umene
    • Yuya Nogami
    • Kenta Masuda
    • Yusuke Kobayashi
    • Eiichiro Tominaga
    • Daisuke Aoki
  • View Affiliations

  • Published online on: November 16, 2015     https://doi.org/10.3892/or.2015.4421
  • Pages: 607-613
  • Copyright: © Takeda et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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February-2016
Volume 35 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Takeda T, Banno K, Okawa R, Yanokura M, Iijima M, Irie‑Kunitomi H, Nakamura K, Iida M, Adachi M, Umene K, Umene K, et al: ARID1A gene mutation in ovarian and endometrial cancers (Review). Oncol Rep 35: 607-613, 2016
APA
Takeda, T., Banno, K., Okawa, R., Yanokura, M., Iijima, M., Irie‑Kunitomi, H. ... Aoki, D. (2016). ARID1A gene mutation in ovarian and endometrial cancers (Review). Oncology Reports, 35, 607-613. https://doi.org/10.3892/or.2015.4421
MLA
Takeda, T., Banno, K., Okawa, R., Yanokura, M., Iijima, M., Irie‑Kunitomi, H., Nakamura, K., Iida, M., Adachi, M., Umene, K., Nogami, Y., Masuda, K., Kobayashi, Y., Tominaga, E., Aoki, D."ARID1A gene mutation in ovarian and endometrial cancers (Review)". Oncology Reports 35.2 (2016): 607-613.
Chicago
Takeda, T., Banno, K., Okawa, R., Yanokura, M., Iijima, M., Irie‑Kunitomi, H., Nakamura, K., Iida, M., Adachi, M., Umene, K., Nogami, Y., Masuda, K., Kobayashi, Y., Tominaga, E., Aoki, D."ARID1A gene mutation in ovarian and endometrial cancers (Review)". Oncology Reports 35, no. 2 (2016): 607-613. https://doi.org/10.3892/or.2015.4421