ARID1A Mutations and PI3K/AKT Pathway Alterations in Endometriosis and Endometriosis-Associated Ovarian Carcinomas
Endometriosis is a common gynecological disease affecting 6%–10% of women of reproductive age and is characterized by the presence of endometrial-like tissue in localizations outside of the uterine cavity as, e.g., endometriotic ovarian cysts. Mainly, two epithelial ovarian carcinoma subtypes, the o...
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doaj-af4f22ad02aa439fa8c4c9f24fd2bc422020-11-24T23:07:49ZengMDPI AGInternational Journal of Molecular Sciences1422-00672013-09-01149188241884910.3390/ijms140918824ARID1A Mutations and PI3K/AKT Pathway Alterations in Endometriosis and Endometriosis-Associated Ovarian CarcinomasPatrick ImeschDaniel FinkKonstantin J. DedesAurelia NoskeEleftherios P. SamartzisEndometriosis is a common gynecological disease affecting 6%–10% of women of reproductive age and is characterized by the presence of endometrial-like tissue in localizations outside of the uterine cavity as, e.g., endometriotic ovarian cysts. Mainly, two epithelial ovarian carcinoma subtypes, the ovarian clear cell carcinomas (OCCC) and the endometrioid ovarian carcinomas (EnOC), have been molecularly and epidemiologically linked to endometriosis. Mutations in the gene encoding the AT-rich interacting domain containing protein 1A (ARID1A) have been found to occur in high frequency in OCCC and EnOC. The majority of these mutations lead to a loss of expression of the ARID1A protein, which is a subunit of the SWI/SNF chromatin remodeling complex and considered as a bona fide tumor suppressor. ARID1A mutations frequently co-occur with mutations, leading to an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, such as mutations in PIK3CA encoding the catalytic subunit, p110α, of PI3K. In combination with recent functional observations, these findings strongly suggest cooperating mechanisms between the two pathways. The occurrence of ARID1A mutations and alterations in the PI3K/AKT pathway in endometriosis and endometriosis-associated ovarian carcinomas, as well as the possible functional and clinical implications are discussed in this review.http://www.mdpi.com/1422-0067/14/9/18824endometriosisovarian clear cell carcinoma (OCCC)endometrioid ovarian carcinoma (EnOC)ARID1API3K/AKT pathwayPIK3CA |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Patrick Imesch Daniel Fink Konstantin J. Dedes Aurelia Noske Eleftherios P. Samartzis |
spellingShingle |
Patrick Imesch Daniel Fink Konstantin J. Dedes Aurelia Noske Eleftherios P. Samartzis ARID1A Mutations and PI3K/AKT Pathway Alterations in Endometriosis and Endometriosis-Associated Ovarian Carcinomas International Journal of Molecular Sciences endometriosis ovarian clear cell carcinoma (OCCC) endometrioid ovarian carcinoma (EnOC) ARID1A PI3K/AKT pathway PIK3CA |
author_facet |
Patrick Imesch Daniel Fink Konstantin J. Dedes Aurelia Noske Eleftherios P. Samartzis |
author_sort |
Patrick Imesch |
title |
ARID1A Mutations and PI3K/AKT Pathway Alterations in Endometriosis and Endometriosis-Associated Ovarian Carcinomas |
title_short |
ARID1A Mutations and PI3K/AKT Pathway Alterations in Endometriosis and Endometriosis-Associated Ovarian Carcinomas |
title_full |
ARID1A Mutations and PI3K/AKT Pathway Alterations in Endometriosis and Endometriosis-Associated Ovarian Carcinomas |
title_fullStr |
ARID1A Mutations and PI3K/AKT Pathway Alterations in Endometriosis and Endometriosis-Associated Ovarian Carcinomas |
title_full_unstemmed |
ARID1A Mutations and PI3K/AKT Pathway Alterations in Endometriosis and Endometriosis-Associated Ovarian Carcinomas |
title_sort |
arid1a mutations and pi3k/akt pathway alterations in endometriosis and endometriosis-associated ovarian carcinomas |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2013-09-01 |
description |
Endometriosis is a common gynecological disease affecting 6%–10% of women of reproductive age and is characterized by the presence of endometrial-like tissue in localizations outside of the uterine cavity as, e.g., endometriotic ovarian cysts. Mainly, two epithelial ovarian carcinoma subtypes, the ovarian clear cell carcinomas (OCCC) and the endometrioid ovarian carcinomas (EnOC), have been molecularly and epidemiologically linked to endometriosis. Mutations in the gene encoding the AT-rich interacting domain containing protein 1A (ARID1A) have been found to occur in high frequency in OCCC and EnOC. The majority of these mutations lead to a loss of expression of the ARID1A protein, which is a subunit of the SWI/SNF chromatin remodeling complex and considered as a bona fide tumor suppressor. ARID1A mutations frequently co-occur with mutations, leading to an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, such as mutations in PIK3CA encoding the catalytic subunit, p110α, of PI3K. In combination with recent functional observations, these findings strongly suggest cooperating mechanisms between the two pathways. The occurrence of ARID1A mutations and alterations in the PI3K/AKT pathway in endometriosis and endometriosis-associated ovarian carcinomas, as well as the possible functional and clinical implications are discussed in this review. |
topic |
endometriosis ovarian clear cell carcinoma (OCCC) endometrioid ovarian carcinoma (EnOC) ARID1A PI3K/AKT pathway PIK3CA |
url |
http://www.mdpi.com/1422-0067/14/9/18824 |
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