The roles of ARID1A in gynecologic cancer

Abstract

One of the exciting findings in recent cancer genome studies is the discovery of somatic mutations in several chromatin remodeling genes. These studies not only illuminate the emerging roles of chromatin remodeling in the pathogenesis of human cancer but also provide molecular genetic basis of aberrant epigenomic regulation as one of the key mechanisms driving cancer development. This is because chromatin remodeling influences a variety of DNA activities such as replication, transcription, repair, methylation, and recombination. Among the mutated chromatin remodeling genes reported, ARID1A is frequently mutated in a variety of human cancers, especially in endometrium-related neoplasms including ovarian clear cell carcinoma, ovarian endometrioid carcinomas, and uterine endometrioid carcinomas, all of which arise from endometrial epithelium. This review will summarize the recent advances in studying the roles of ARID1A mutations in gynecologic cancers with special emphasis on how this new knowledge will further extend our understanding of the pathogenesis of endometrium-related carcinomas.

Keywords: ARID1A; BAF250a; Chromatin remodeling; Endometriosis; Ovarian cancer.

Fig. 1

Immunohistochemical study of an endometrial endometrioid carcinoma with coexisting high-grade (A) and low-grade (B, C) components. The high-grade component is negative for ARID1A (D) while the low-grade component has areas with retained ARID1A staining (E) and areas with clonal loss of ARID1A (F) (A-F, ×200).