Regional DNA hypermethylation and DNA methyltransferase (DNMT) 1 protein overexpression in both renal tumors and corresponding nontumorous renal tissues

Eri Arai, Yae Kanai, Saori Ushijima, Hiroyuki Fujimoto, Kiyoshi Mukai, Setsuo Hirohashi

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

To evaluate the significance of altered DNA methylation during renal tumorigenesis, tumorous tissues (T) and corresponding non-tumorous renal tissues (N) from 94 patients with renal tumors, and normal renal tissues (C) from 16 patients without renal tumors were investigated. DNA methylation status on CpG islands of the p16, human MutL homologue 1 (hMLH1), von-Hippel Lindau (VHL) and thrombospondin-1 (THBS-1) genes and the methylated in tumor (MINT) -1, -2, -12, -25 and -31 clones and DNA methyltransferase (DNMT) 1 expression were examined by bisulfite modification and immunohistochemistry, respectively. The average number of methylated CpG islands was significantly higher in N than in C, and was even higher in T. The average number of methylated CpG islands in N was significantly correlated with a higher histological grade of corresponding conventional renal cell carcinomas (RCCs). The average number of methylated CpG islands in RCCs was significantly correlated with macroscopic configuration with extranodular or multinodular growth, higher histological grade, infiltrating growth pattern and vascular involvement. The recurrence-free survival rate of patients with RCCs showing accumulation of DNA methylation was significantly lower than that of patients not showing this feature. The incidence of nuclear immunoreactivity for DNMT1 tended to be higher in proximal tubules from N than in those from C, and was significantly higher in RCCs. From the viewpoint of altered DNA methylation, N is at the precancerous stage, and N showing accumulation of DNA methylation may generate more malignant RCCs. Regional DNA hypermethylation may be associated with renal tumorigenesis from a precancerous condition to malignant progression and become a predictor of patient prognosis.

Original languageEnglish
Pages (from-to)288-296
Number of pages9
JournalInternational Journal of Cancer
Volume119
Issue number2
DOIs
Publication statusPublished - 2006 Jul 15
Externally publishedYes

Keywords

  • DNA methylation
  • DNA methyltransferase 1
  • Multistage tumorigenesis
  • Precancerous condition
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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