Correlation of postoperative recurrence in hepatocellular carcinoma with demethylation of repetitive sequences.
Restriction landmark genomic scanning (RLGS) was utilized to identify novel genomic alterations in hepatocellular carcinoma (HCC). Thirty-one HCC samples were examined by RLGS. Two high intensity spots were common to several RLGS profiles of different HCCs. Nucleotide sequencing and homology search analysis showed that these spots represented repetitive sequences, Human tandem repeat sequence (Genbank, L09552) and centromeric NotI cluster (Genbank, Y10752). These intensified signals were attributable to the occurrence of demethylated areas in the recognition sequence of the NotI site of the corresponding fragments. The intensity of these spots in the RLGS profile reflects their degree of demethylation, which was significantly correlated with postoperative recurrence, even in patients regarded as belonging to the good prognosis group by conventional prognostic factors. Multivariate analysis showed that the intensities of the two spots retained independent prognostic value. This is a new type of predictive factor for HCC based on epigenetic changes in hepatocarcinogenesis, and in the future it is expected to be of great value in making preoperative diagnosis and selecting postoperative therapy.
Itano
Osamu
O
Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Ueda
Masakazu
M
Kikuchi
Kiyoshi
K
Hashimoto
Osamu
O
Hayatsu
Shigeo
S
Kawaguchi
Masaharu
M
Seki
Hiroaki
H
Aiura
Kouichi
K
Kitajima
Masaki
M
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics; D011184:Postoperative Period; D011379:Prognosis; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; D020080:Tandem Repeat Sequences; D016896:Treatment Outcome