Extensive methylation is associated with β-Catenin mutations in hepatocellular carcinoma: Evidence for two distinct pathways of human hepatocarcinogenesis

Naoshi Nishida, Takafumi Nishimura, Takeshi Nagasaka, Iwao Ikai, Goel Ajay, C. Richard Roland

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Hepatocellular carcinoma (HCC) with p53 mutations is usually characterized by extensive chromosomal instability (CIN), whereas those with β-catenin mutations have relatively less CIN and the molecular pathogenesis of these tumors is unknown. Methylation of CpG dinucleotides in the promoters of cancer-related genes is another characteristic feature of HCCs. The aim of this study was to determine the contribution of the methylator phenotype to HCC and its relationship to genomic instability. Fractional allelic loss (FAL) was determined using 400 microsatellite markers in 81 HCCs and 77 corresponding noncancerous livers as a measure of CIN. Methylation of 21 genetic loci was quantitated using combined bisulfite restriction analysis. Using hierarchical clustering analysis based upon the quantification of methylation levels, all HCCs were segregated into two groups characterized by either limited or extensive methylation. Mutations in the β-catenin and p53 genes were determined by DNA sequencing. We found that the methylation levels were significantly higher in the HCCs than in noncancerous livers in 18 of the 21 loci (P values ranged from 0.035 to

Original languageEnglish
Pages (from-to)4586-4594
Number of pages9
JournalCancer Research
Volume67
Issue number10
DOIs
Publication statusPublished - May 15 2007
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this