CHFR Promoter Hypermethylation and Reduced CHFR mRNA Expression in Ovarian Cancer

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Abstract
Ovarian cancer is one of the most common cancers and can be treated with microtubule-targeting drugs. Checkpoint with forkhead and ring finger domains (CHFR) is a protein implicated in cancer sensitivity to microtubule-targeting drugs. Whereas CHFR downregulation, often with CHFR promoter hypermethylation, has been identified in a large number of tumor types, it has not been in ovarian cancer. We therefore searched for CHFR downregulation in primary ovarian tumors. Fresh ovarian cancer tissues from 53 patients (test) and normal ovarian tissues from 21 patients (control) were tested for CHFR promoter hypermethylation and CHFR mRNA levels. The CHFR promoter was hypermethylated in 20.75% (11/53) of the ovarian cancers and none (0/21) of the normal controls. The normal controls had a mean mRNA level of 1.89 relative fluorescence units (RFU) with a range of 0.04–24.78 RFU. The cancer tissues had a mean mRNA level of 0.77 RFU with a range of 0.00–68.75 RFU. The median value of the cancer group was significantly lower than that of the control group (p=0.0067). Those cancer samples that had hypermethylated CHFR promoters also had low (n=3) or undetectable (n=8) CHFR mRNA levels. In contrast to previous reports, we found that alterations in CHFR mRNA and CHFR methylation can be frequently found in ovarian cancers. CHFR hypermethylation was strongly associated with the loss of CHFR mRNA expression. CHFR downregulation in ovarian tumors may be clinically relevant as a staging biomarker, as an indicator of sensitivity to microtubule-targeting drugs, and as a future drug target.

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