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Cancer-Testis Antigen Expression in Serous Endometrial Cancer with Loss of X Chromosome Inactivation
Authors:Jun Kang  Hee Jin Lee  Sun-Young Jun  Eun Su Park  Lee-so Maeng
Affiliation:1. Department of Hospital Pathology, Incheon St. Mary''s Hospital, College of Medicine, The Catholic University of Korea, Inchun, Republic of Korea.; 2. Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.; IRCCS National Cancer Institute, ITALY,
Abstract:

Background

Cancer-testis antigens (CTAs) are potential targets for cancer immunotherapy. Many CTAs are located on the X chromosome and are epigenetically regulated. Loss of X chromosome inactivation (XCI) is observed in breast and ovarian cancers and is thought to be related to the overexpression of CTAs. We investigated the relation between expression of CTAs and loss of XCI in endometrial cancer.

Materials and Methods

We used data generated by The Cancer Genome Atlas Genome Data Analysis Centers and data for Xist knockout mice available at the Gene Expression Omnibus.

Results

The status of XCI was estimated by methylation status, and deletion or gain of the X chromosome. The endometrial cancers were classified into the following three groups: preserved inactivated X chromosome (Xi) (n = 281), partial reactivation of Xi (n = 52), and two copies of active X group (n = 38). Loss of XCI was more common in serous adenocarcinoma. Expression of CTAs increased in endometrial cancer with loss of XCI, which was accompanied by global hypomethylation. Expression of CTAs did not increase in Xist knockout mice.

Conclusions

Loss of XCI is common in serous adenocarcinoma. Global hypomethylation, and not loss of XCI, is the main mechanism of overexpression of CTAs.
Keywords:
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