CHFR promoter hypermethylation and reduced CHFR mRNA expression in ovarian cancer.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Gao
Ying
Y
Department of Gynecology, Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Lou
Ge
G
Zhang
Guang-Mei
GM
Sun
Xi-Wen
XW
Ma
Yu-Yan
YY
Yang
Yan-Mei
YM
Liu
Ge
G
D000328:Adult; D000368:Aged; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D044767:Ubiquitin-Protein Ligases
D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D012333:RNA, Messenger; C412002:CHFR protein, human; D044767:Ubiquitin-Protein Ligases