Adenine thymine-rich interactive domain 1A (ARIDIA) gene is a non-catalytical unit of Switch/Sucrose nonfermenting (SWI/SNF) chro-matin-remodeling complex, which encodes the BRG1-related factor 250a (BAF250a
expression in atypical endometriosis and endometriosis-associated ovarian cancer.
For example, ARID1A, identified as a tumor suppressor gene, encodes BAF250a
, a key component of the SWI-SNF chromatin remodeling complex.
Ovarian cancers arising from endometriosis: a microenvironmental biomarker study including ER, HNF1ss, p53, PTEN, BAF250a
, and COX-2.
ARID1A, which encodes the BAF250A tumor suppressor, is somatically mutated in 40% of low-grade endometrioid endometrial carcinomas [reviewed in (24)].
Increased amounts of the cell cycle proteins cyclin E and p16, amplification and overexpression of the ERBB2 [v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2] gene (which encodes the ERBB2 receptor tyrosine kinase), loss of BAF250A production, and altered amounts of the cell adhesion proteins claudin-3, claudin-4, L1CAM (L1 cell adhesion molecule), EpCAM (epithelial cell adhesion molecule), and E-cadherin have also been documented [reviewed in (24)].
Apart from the morphologic and clinical features separating type 1 from type 2 ECs, they are further distinguished by specific genetic alterations ; EECs are characterized by microsatellite instability (MSI), somatic alterations within the PI3K pathway and the MAPK pathway, and mutations of CTNNB1 ([beta]-catenin) and ARID1A (BAF250a
Loss of BAF250a
expression was seen in 42% of the ovarian clear cell carcinoma samples and 21% of the endometrioid carcinoma samples, compared with just 1% of the high-grade serous carcinoma samples.
ARIDlA (AT-rich interactive domain 1A), also known as BAF250A
and SMARCFl, is a member of the switch/sucrose nonfermentable, ATP-dependent family of chromatin-restructuring genes that are involved in epigenetic regulation and are collectively mutated in approximately 20% of all malignancies.
Lastly, while PTEN, BAF250a
, and DNA mismatch repair testing may be helpful for differentiating endometrioid from serous carcinoma, these are of less use in differentiating clear cell from serous carcinoma because expression of those markers does not significantly differ between the 2 carcinomas.
(5,27-29) Most recently, mutation of the ARID1A gene and loss of the corresponding protein BAF250a has also been implicated in the pathogenesis of endometrioid carcinomas.
(34) In addition, E-cadherin alterations (reduced or absent expression), abnormal p16 expression, loss of BAF250a, and somatic mutations of the protein phosphatase 2 regulatory protein-1A (PPP2R1A) have also been found in USC.