ARID1A gene mutation in ovarian and endometrial cancers (Review)

Takeda, Takashi; Banno, Kouji; Okawa, Ryuichiro; Yanokura, Megumi; Iijima, Moito; Irie-Kunitomi, Haruko; Nakamura, Kenzo; Iida, Miho; Adachi, Manabu; Umene, Kiyoko; Nogami, Yuya; Masuda, Kenta; Kobayashi, Yusuke; Tominaga, Eiichiro; Aoki, Daisuke

doi:10.3892/or.2015.4421

Cited by 158 publications

(131 citation statements)

References 70 publications

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“…Furthermore, ARID1A mutations and BAF250a deficits were identified in OCCC and adjacent endometriotic lesions, but not in distant lesions, which suggests that this mutation and resultant BAF250a deficit are events in the early stage of neoplastic transformation of endometriosis (2,42). A previous study confirmed that an ARID1A deficit was also an early phenomenon in endometriosis-associated ovarian cancer (EAOC) and endometriotic ovarian cysts, together with AKT protein activation and a histone H2A variant (γH2AX) (43).…”

Section: Aberrant Chromatin Remodeling and Ovarian Cancersupporting

confidence: 65%

“…In 22 patients with uterine CS, Jones et al (57) revealed ARID1A mutations in 8 (36%) cases, mutations of histone methyltransferase MLL3 in 6 (27%) cases, mutations of speckle-type POZ protein (SPOP), which is involved in chromatin remodeling, in 3 (14%) cases, and mutations of chromatin remodeling-associated genes in 14 (64%) cases (57). ARID1A serves an important role in the regulation of cell growth, and MLL3 is a coactivator of tumor protein p53 (TP53), a tumor suppressor p53 gene (2,58). SPOP is a transcriptional repressor of p53 via the bric-a-brac/tramtrack/broad complex protein (59).…”

Section: Aberrant Chromatin Remodeling and Endometrial Cancermentioning

confidence: 99%

“…The term 'chromatin remodeling' refers to the alteration of chromatin structure from a closed state to a loosened one, which is termed 'euchromatin' (1). There are a few types of chromatin remodeling complexes, including the SWItch/sucrose non-fermentable (SWI/SNF) complex, which has several subunits, including ARID1A and brahma homologue (BRM)-related gene 1 (BRG1; also referred to as SMARCA4) (2). Through the interaction between subunits, chromatin remodeling complexes change chromatin structure, and this determines gene expression levels via the regulation of the interaction between proteins with double-stranded DNA (3).…”

Section: Introductionmentioning

confidence: 99%

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Aberrant chromatin remodeling in gynecological cancer (Review)

et al. 2017

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Abstract. Epigenetic regulatory mechanisms are a current focus in studies investigating cancer. Chromatin remodeling alters chromatin structure and regulates gene expression, and aberrant chromatin remodeling is involved in carcinogenesis. AT-rich interactive domain-containing protein 1A (ARID1A) and SWItch/sucrose non-fermentable-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 are remodeling factors that are mutated in numerous types of cancer. In gynecological cancer, ARID1A mutations have been identified in 46-57% of clear cell carcinoma and 30% of endometrioid carcinoma. Mutations of chromodomain helicase, DNA-binding protein 4 have been detected in 17-21% of endometrial serous cancer, and mutations of ARID1A and mixed-lineage leukemia 3 occur in 36 and 27% of uterine carcinosarcoma, respectively. These data suggest that aberrant chromatin remodeling is a potential cause of cancer, and have led to the development of novel proteins targeting these processes. Additional accumulation of information on the mechanisms of chromatin remodeling and markers for these events may promote personalized anticancer therapies.

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Section: Aberrant Chromatin Remodeling and Ovarian Cancersupporting

confidence: 65%

Section: Aberrant Chromatin Remodeling and Endometrial Cancermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Aberrant chromatin remodeling in gynecological cancer (Review)

et al. 2017

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“…22 Recently, it has also been suggested that ARID1A mutations may be targeted by EZH2 inhibitors that are currently in development. 23 Consequently, the first priority for further research in this molecular subtype is more extensive sequencing with methods such as whole-exome sequencing, RNA sequencing, and whole-genome sequencing to discover novel genomic events affecting kinases that could suggest therapeutic vulnerabilities.…”

Section: Discussionmentioning

confidence: 99%

Molecular Subtypes ofKIT/PDGFRAWild-Type Gastrointestinal Stromal Tumors

et al. 2016

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IMPORTANCE Wild-type (WT) gastrointestinal stromal tumors (GISTs), which lack KIT and PDGFRA gene mutations, are the primary form of GIST in children and occasionally occur in adults. They respond poorly to standard targeted therapy. Better molecular and clinical characterization could improve management. OBJECTIVE To evaluate the clinical and tumor genomic features of WT GIST. DESIGN, SETTING, AND PARTICIPANTS Patients enrolled in an observational study at the National Institutes of Health starting in 2008 and were evaluated in a GIST clinic held once or twice yearly. Patients provided access to existing medical records and tumor specimens. Self-referred or physician-referred patients younger than 19 years with GIST or 19 years or older with known WT GIST (no mutations in KIT or PDGFRA) were recruited; 116 patients with WT GIST were enrolled, and 95 had adequate tumor specimen available. Tumors were characterized by immunohistochemical analysis (IHC) for succinate dehydrogenase (SDH) subunit B, sequencing of SDH genes, and determination of SDHC promoter methylation. Testing of germline SDH genes was offered to consenting patients and families. MAIN OUTCOMES AND MEASURES For classification, tumors were characterized by SDHA, B, C, or D (SDHX) mutations and other genetic and epigenetic alterations, including presence of mutations in germline. Clinical characteristics were categorized. RESULTS Wild-type GIST specimens from 95 patients (median age, 23 [range, 7–78] years; 70% female) were classified into 3 molecular subtypes: SDH-competent (n = 11), defined by detection of SDHB by IHC; and 2 types of SDH-deficient GIST (n = 84). Of SDH-deficient tumors, 63 (67%) had SDH mutations, and in 31 of 38 (82%), the SDHX mutation was also present in germline. Twenty-one (22%) SDH-deficient tumors had methylation of the SDHC promoter leading to silencing of expression. Mutations in known cancer-associated pathways were identified in 9 of 11 SDH-competent tumors. Among patients with SDH-mutant tumors, 62% were female (39 of 63), median (range) age was 23 (7–58) years, and approximately 30% presented with metastases (liver [12 of 58], peritoneal [6 of 58], lymph node [15 of 23]). SDHC-epimutant tumors mostly affected young females (20 of 21; median [range] age, 15 [8–50] years), and approximately 40% presented with metastases (liver [7 of 19], peritoneal [1 of 19], lymph node [3 of 8]). SDH-deficient tumors occurred only in the stomach and had an indolent course. CONCLUSIONS AND RELEVANCE An observational study of WT GIST permitted the evaluation of a large number of patients with this rare disease. Three molecular subtypes with implications for prognosis and clinical management were identified.

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“…ARID1A knockout mice do not develop ovarian tumors, whereas 60% with a double ARID1A/PTEN knockout develop ovarian cancers. 24,25 Therefore, in AE and to a lesser extent typical endometriosis, critical molecular aberrations develop that predispose to cancer. Further research is needed to find biomarkers that identify patients with endometriotic lesions at high risk for developing EaOC.…”

Section: Discussionmentioning

confidence: 99%