Decreased Expression of the ARID1A Gene Is Associated with Poor Prognosis in Primary Gastric Cancer

Wang, Dan Dan; Chen, Yi Bing; Pan, Ke; Wei, Wang; Chen, Shi Ping; Chen, Ju gao; Zhao, Jing; Lv, Lin; Pan, Qiu Zhong; Li, Yong Qiang; Wang, Qi Jing; Huang, Li Xi; Ke, Miao La; He, Jia; Xia, Jian Chuan

doi:10.1371/journal.pone.0040364

Cited by 92 publications

(126 citation statements)

References 24 publications

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“…Loss of ARID1A expression was found to be an adverse prognostic factor in gastric cancer, 9 cervical cancer 33 and endometrial clear cell carcinoma. 6 In ovarian clear cell carcinoma, the prognostic effects of ARID1A expression were inconsistent in different studies by Shih et al 10 and Katagiri et al 34 Both our study and Shih's study revealed that ARID1A expression was not a prognostic factor for ovarian clear cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…4 ARID1A is a tumorsuppressor gene located at 1p36, which is frequently mutated in ovarian, endometrial, breast, urinary bladder and gastric cancers. [5][6][7][8][9] In gynecologic cancers, ARID1A promotes formation of SWI/SNFmediated chromatin remodeling and is present in 46% of ovarian clear cell carcinomas and 30% of endometrioid carcinomas. 5,24 In our study, we confirmed that loss of ARID1A expression was cell carcinoma, and can be caused by either PIK3CA mutations, PTEN loss or a combination of these alterations.…”

Section: Discussionmentioning

confidence: 99%

“…4 In humans, ARID1A is a tumorsuppressor gene located at 1p36, which is frequently mutated in ovarian, endometrial, breast, urinary bladder and gastric cancers. [5][6][7][8][9] ARID1A mutations are present in 46% of ovarian clear cell carcinomas and 30% of endometrioid carcinomas. 5 ARID1A immunohistochemistry (IHC) is closely related to ARID1A mutational status, 10 and can be used as a surrogate marker for ARID1A mutation.…”

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Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma

et al. 2014

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AT-rich interactive domain 1A (ARID1A) is a subunit of switch/sucrose non-fermentable (SWI/SNF) complex. Recently, alterations of ARID1A gene, phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway and zinc-finger protein 217 (ZNF217) gene have been identified as frequent molecular genetic changes in ovarian clear cell carcinoma. The relationships between these events have not been studied and integrated in the same cohort. This study was aimed at determining the correlation between these molecular events and other clinicopathological factors, including the prognostic impacts of these clinicopathological factors. A total of 68 ovarian clear cell carcinoma cases were collected and subjected to immunohistochemistry testing for ARID1A, SMARCA2, SMARCA4, SMARCB1 and phosphatase and tensin homolog (PTEN), mutation analysis for phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene and fluorescence in situ hybridization for ZNF217 amplification. The correlations between ARID1A expression, PI3K-Akt pathway, ZNF217 amplification and other clinicopathological factors were analyzed. Loss of ARID1A expression was present in 35 cases (52%) and loss of SMARCA2 expression occurred in 1 case. SMARCA4 and SMARCB1 expressions were preserved in all cases. PIK3CA mutations were present in 23 cases (34%) and loss of PTEN expression occurred in 8 cases (12%). Alterations in the PI3K-Akt pathway (PIK3CA mutations or loss of PTEN expression) were found in 42 cases (62%). ZNF217 amplification was detected in 21 cases (31%). Loss of ARID1A expression was significantly related to younger patient age (P ¼ 0.048), PI3K-Akt pathway activation (P ¼ 0.046) and ZNF217 amplification (P ¼ 0.028). All of the clinicopathological factors were not prognostic factors for ovarian clear cell carcinoma after multivariate analysis, except International Federation of Gynecology and Obstetrics staging (P ¼ 0.001). Our results showed that loss of ARID1A expression usually coexisted with PI3K-Akt pathway activation and/or ZNF217 amplification. Synergic effects of loss of ARID1A and PI3K-Akt pathway activation as well as ZNF217 amplification may be related to the development of ovarian clear cell carcinoma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma

et al. 2014

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“…55 In gastric cancer, knockdown of wild-type ARID1A in four gastric cancer cell lines enhanced proliferation, whereas restoring ARID1A expression suppressed tumor proliferation in three ARID1A-deleted gastric cancer cell lines. 45,75 In bile duct cancer, silencing of ARID1A in three cell lines with wild-type ARID1A resulted in increased proliferation, which was reversed when ARID1A was re-expressed ectopically. 51 In hepatocellular carcinoma, ARID1A knockdown significantly promoted cellular proliferation of four wild-type cell lines but did not affect a cell line with ARID1A mutation.…”

Section: Arid1a As a Gatekeepermentioning

confidence: 99%

The emerging roles of ARID1A in tumor suppression

Wang

Shih

2014

Cancer Biology & Therapy

223

187

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“…In gastric cancer, an association has been described between MSI and mutations in ARID1A. 12,[14][15][16] As the rate of somatic ARID1A mutations in MSI cases was 12-to 61-fold higher than the global background mutation rate, it was suggested that the ARID1A gene is particularly targeted by MSI. 12 A possible association between ARID1A loss and MSI, as has been reported for gastric cancer, has not been studied in endometrial cancer.…”

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Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations, TP53 and microsatellite instability in endometrial cancer

et al. 2013

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The switch/sucrose non-fermentable (SWI/SNF) subunit ARID1A (AT-rich interactive domain 1A gene) has been recently postulated as a novel tumor suppressor of gynecologic cancer and one of the driver genes in endometrial carcinogenesis. However, specific relationships with established molecular alterations in endometrioid endometrial cancer (EEC) are currently unknown. We analyzed the expression of ARID1A in 146 endometrial cancers (130 EECs and 16 non-EECs) in relation to alterations in the PI3K-Akt pathway (PTEN expression/KRAS/PIK3CA mutations), TP53 status (TP53 immunohistochemistry) and microsatellite instability. To discriminate between microsatellite instability due to somatic MLH1 promoter hypermethylation or germline mutations in one of the mismatch repair genes (Lynch syndrome), we included a 'Lynch syndrome set'. This set included 21 cases with confirmed germline mutations and 15 cases that were suspected to have a germline mutation. Loss of ARID1A expression was exclusively found in EECs in 31% (40/130) of the EEC cases. No loss of expression of the other subunits of the SWI/SNF complex, SMARCD3 and SMARCB1, was detected. Alterations in the PI3K-Akt pathway were more frequent when ARID1A expression was lost. Loss of ARID1A and mutant-like TP53 expression was nearly mutually exclusive (P ¼ 0.0004). In contrast to Lynch-associated tumors, a strong association between ARID1A loss and sporadic microsatellite instability was found. Only five cases (14%) of the 'Lynch syndrome set' as compared with 24 cases (75%, Po0.0001) of the sporadic microsatellite-unstable tumors showed loss of ARID1A. These observations suggest that ARID1A is a causative gene, instead of a target gene, of microsatellite instability by having a role in epigenetic silencing of the MLH1 gene in endometrial cancer. Keywords: ARID1A; endometrial cancer; Lynch syndrome; microsatellite instability Recent genome-wide sequencing studies have demonstrated that the AT-rich interactive domain 1A (ARID1A) gene is frequently mutated in a wide variety of cancer types 1 including a subset of gynecological cancers. 2 In ovarian cancer, near half of the clear-cell subtype and 30% of the endometrioid subtype showed ARID1A mutations, 3 particularly those that are related to endometriosis. 4,5 In endometrial cancer, mutations in the ARID1A gene have been reported in approximately 30% of both low-and high-grade endometrioid endometrial cancers (EECs) but not in serous endometrial carcinomas. [6][7][8] ARID1A encodes a large nuclear protein involved in chromatin remodeling and interacts with several other proteins, including the core protein

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Decreased Expression of the ARID1A Gene Is Associated with Poor Prognosis in Primary Gastric Cancer

Cited by 92 publications

References 24 publications

Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma

Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma

The emerging roles of ARID1A in tumor suppression

Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations, TP53 and microsatellite instability in endometrial cancer

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