Korean J Urol.  2009 May;50(5):432-438.

The Relationship between RUNX3 Inactivation and Its Pathological Features in Renal Cell Carcinoma

• Kwon WA
• Park C
• Kim EJ
• Ha YS
• Kim YJ
• Yun SJ
• Lee SC
• Kim WJ

Abstract

PURPOSE: DNA methylation is a key regulator of gene transcription and genomic stability, and alterations in DNA methylation are frequently detected in human tumors. Recent study has suggested that inactivation of runt-related transcription factor 3 (RUNX3), primarily epigenetic alterations in DNA methylation, is closely associated with bladder tumor stage, grade, and prognosis. The aim of this study was to evaluate the association between RUNX3 inactivation and renal cell carcinoma (RCC).
MATERIALS AND METHODS
RCC tissues (n=56) were obtained from patients who underwent radical nephrectomy. The methylation pattern of RUNX3 was determined by using methylation specific-polymerase chain reaction (MS-PCR) and direct DNA sequencing.
RESULTS
Methylation of the RUNX3 promoter was observed in 75.0% of the samples (42/56). The tumor stage and grade were significantly associated with the methylation status (p<0.05, respectively). However, recurrence and progression of RCC were not significantly related to the methylation of the RUNX3 promoter region (log-rank test, p>0.05, respectively).
CONCLUSIONS
This study demonstrated that promoter methylation of RUNX3 is frequently observed in RCC. In addition, RUNX3 methylation is closely associated with aggressive pathologic features.

Keyword

Human RUNX3 protein; Methylation; Renal cell carcinoma

MeSH Terms

Carcinoma, Renal Cell
DNA Methylation
Epigenomics
Genomic Instability
Humans
Methylation
Nephrectomy
Prognosis
Promoter Regions, Genetic
Recurrence
Sequence Analysis, DNA
Transcription Factor 3
Urinary Bladder Neoplasms
Transcription Factor 3

Figure

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  Fig. 1 Nucleotide sequence of runt-related transcription factor 3 (RUNX3) promoter region. Nucleotide sequence from -880 to +1 region is shown. CpG dinucleotides are marked in bold.

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  Fig. 2 Methylation of the runt-related transcription factor 3 (RUNX3) promoter region in renal cell carcinoma (RCC) cell lines. DNA from 5 RCC cell lines was analyzed by methylation specific polymerase chain reaction (PCR) followed by direct DNA sequencing. Methylated CpG cytosines remained as cytosines, whereas unmethylated cytosines changed to thymidines in the PCR products.

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