High frequency of promoter hypermethylation of RASSF1A in tumor and plasma of patients with hepatocellular carcinoma.
OBJECTIVE
To determine the presence of ras association domain family 1A (RASSF1A) promoter methylation in the tumor tissues and plasma of patients with hepatocellular carcinoma (HCC).


METHODS
Methylation-specific polymerase chain reaction was used to detect RASSF1A methylation in DNA extracted from HCC tumors and paired plasma samples of 40 patients. The association of RASSF1A hypermethylation in tumor and plasma DNA of HCC patients with clinicopathological characteristics was also analyzed.


RESULTS
RASSF1A promoter hypermethylation was detected in 37 of the 40 HCC tissues (92.5%). Of the paired plasma from the 40 HCC patients, aberrant methylation was detected in 17 (42.5%). No RASSF1A methylation was detected in the plasma in the absence of methylation in the corresponding tumor. The presence of RASSF1A promoter hypermethylation in plasma DNA was found to associate with HCC size of > or =4 cm (P = 0.035).


CONCLUSIONS
RASSF1A promoter hypermethylation occurred at a high frequency in HCC. The aberrant methylation was also detectable in over 40% of matched plasma. The latter should be evaluated as a screening tool and/or prognosticator of HCC patients.
Yeo
Winnie
W
Department of Clinical Oncology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong. winnieyeo@cuhk.edu.hk
Wong
Nathalie
N
Wong
Wai-Lap
WL
Lai
Paul B S
PB
Zhong
Sheng
S
Johnson
Philip J
PJ
D001483:Base Sequence; D001707:Biopsy, Needle; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D011401:Promoter Regions, Genetic; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics*
C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins