Aberrant methylation of the CHFR gene in advanced hepatocellular carcinoma.
OBJECTIVE
Recently, aberrant methylation of the CHFR gene associated with gene silencing has been reported in several cancers. We examined the methylation status of the CHFR gene in primary hepatocellular carcinomas (HCCs) and evaluated the correlation between the methylation status and the malignancy of HCC.


METHODS
We first examined the methylation status of the CHFR promoter region and mRNA expression in cancer cell lines. Next, we examined the methylation status of the CHFR gene in 62 primary HCCs and then investigated the correlation between CHFR methylation and the clinicopathological findings.


RESULTS
The cell line with CHFR promoter methylation showed a loss of CHFR expression that was restored after 5-aza-2'-deoxycytidine (5-aza-dC) treatment, suggesting that aberrant methylation of the CHFR gene was associated with gene silencing. CHFR methylation was detected in 22 of 62 (35%) primary HCCs, whereas no methylation was detected in noncancerous liver tissues. Furthermore, CHFR methylation was significantly associated with an infiltrative growth pattern (p=0.047) and an advanced stage (p=0.037).


CONCLUSIONS
Aberrant methylation of the CHFR gene is significantly correlated with the progression of HCC, suggesting that CHFR methylation might be a novel molecular marker to estimate the malignancy of this disease.
Sakai
Mitsuru
M
Department of Surgery II, Graduate School of Medicine, Nagoya University, Japan.
Hibi
Kenji
K
Kanazumi
Naohito
N
Nomoto
Shuji
S
Inoue
Soichiro
S
Takeda
Shin
S
Nakao
Akimasa
A
D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D016009:Chi-Square Distribution; D002869:Chromosome Aberrations; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D000075223:Poly-ADP-Ribose Binding Proteins; D011336:Probability; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C412002:CHFR protein, human; D044767:Ubiquitin-Protein Ligases