Early warning sign found for endometriosis becoming cancer

November 1, 2010

The AT-rich interactive domain 1A gene is a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas. Because AR1D1A mutation and loss of BAF250a, the protein encoded by AR1D1A, are detectable in preneoplastic lesions, they may herald the transformation of endometriosis into cancer, according to new research.

The AT-rich interactive domain 1A (SWI-like) gene (ARID1A) is a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas. Because ARID1A mutation and loss of BAF250a, the protein encoded by ARID1A, are detectable in preneoplastic lesions, they may herald the transformation of endometriosis into cancer, according to new research.

Researchers in British Columbia, Canada, sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A in 6 of the samples. BAF250a is a key component of the SWI-SNF chromatin remodeling complex. The researchers also sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression in an additional 455 ovarian carcinomas.

The researchers determined that 46% of the women with ovarian clear-cell carcinomas and 30% of the women with endometrioid carcinomas had mutations in ARID1A, whereas no mutations were found in any of the 76 specimens from the women with the high-grade serous ovarian carcinomas. Furthermore, the study team found a decrease in BAF250a expression in 42% of the ovarian clear-cell carcinomas and 21% of the endometrioid carcinomas but in only 1% of the high-grade serous carcinomas.