ARID1A

ARID1A, also known as AT-rich interaction domain-containing protein 1A and BAF250A, is a human gene that encodes a large subunit of the SWI/SNF chromatin remodeling complex. The gene is located on chromosome 1p36.11. The encoded protein contains an ARID DNA-binding domain and functions as a scaffolding subunit that helps recruit and stabilize the SWI/SNF complex on chromatin.

ARID1A is a tumor suppressor gene. It is frequently inactivated in a range of cancers through somatic mutations or deletions, with particularly high relevance in ovarian clear cell carcinoma and endometrioid endometrial carcinoma, as well as in gastric, colorectal, bladder, and hepatocellular carcinomas. Loss of ARID1A disrupts the function of the BAF (SWI/SNF) chromatin remodeling complex, altering chromatin accessibility and gene expression. This can affect processes such as the DNA damage response, cell cycle regulation, and differentiation, contributing to tumorigenesis.

In the SWI/SNF system, ARID1A-containing complexes (BAF-A) are largely mutually exclusive with ARID1B-containing complexes (BAF-B). ARID1A interacts with the catalytic ATPases BRG1 (SMARCA4) or BRM (SMARCA2) and collaborates with other chromatin regulators to modulate transcription. The loss of ARID1A expression in tumors can be detected by sequencing or immunohistochemistry and has become an important biomarker in certain gynecologic cancers.

Therapeutically, ARID1A-mutant cancers show potential vulnerabilities, including sensitivity to EZH2 inhibitors, reflecting a synthetic-lethal relationship between SWI/SNF disruption and Polycomb repressive complex 2 activity. Ongoing research explores additional targeted strategies and diagnostic implications.