Decreased expression and frequent allelic inactivation of the RUNX3 gene at 1p36 in human hepatocellular carcinoma

Abstract

Hypermethylation and LOH appear to be common mechanisms for inactivation of RUNX3 in HCC. Therefore, RUNX3 may be an important tumor suppressor gene related to hepatocarcinogenesis.

Methylation of multiple genes as molecular markers for diagnosis of a small, well‐differentiated hepatocellular carcinoma

“…[5][6][7] Clinical studies investigating associations between carcinogenesis and abnormal methylation on CpG islands in tumor suppressor genes or genes involved in cell proliferation and death have been conducted in various cancers. [8][9][10][11][12] For HCC, it has been reported that some genes undergo hypermethylation in liver tissues, [13][14][15][16][17][18][19][20][21] supporting the hypothesis that determination of methylation in specific genes may be useful for HCC diagnosis. However, to the best of our knowledge, the diagnosis of HCC, in particular early HCC, based on the methylation levels of a single gene has not been clinically investigated to date.…”

“…APC, CASP8, CCND2, CFTR, CDKN2A, GSTP1, HIC1, POU3F1, RASSF1A, RUNX3, SPINT2 and TP73 were the genes filtered and were selected from previously reported data. [13][14][15][16][17][18][19][20][21] With the exception of CASP8, all genes were found to contain CpG islands located in their promoter regions by CpG mapping analysis, and the regions including their short CpG-rich stretches were successfully amplified for methylation analysis by sequencing. For CASP8, the region located in intron 3 that contained several CpG dinucleotide sequences was amplified (Table II).…”

“…However, to the best of our knowledge, the diagnosis of HCC, in particular early HCC, based on the methylation levels of a single gene has not been clinically investigated to date. [13][14][15][16][17][18][19][20][21] The aim of the current study was to identify a combination of methylated marker genes suitable for use in the diagnosis of a small HCCs less than 3 cm HCC or a well-differentiated HCC as an early HCC, and to establish a user-friendly methylation-specific PCR (MSP) system to measure methylation status of these HCC gene markers. To achieve the aim, we selected 12 genes (APC, CASP8, CCND2, CFTR, CDKN2A, GSTP1, HIC1, POU3F1, RASSF1A, RUNX3, SPINT2 and TP73) with a clear methylation in >50% (actually 68-100%) of HCC cases examined in studies reported previously as genetic marker candidates for diagnosis of early HCC.…”

“…To achieve the aim, we selected 12 genes (APC, CASP8, CCND2, CFTR, CDKN2A, GSTP1, HIC1, POU3F1, RASSF1A, RUNX3, SPINT2 and TP73) with a clear methylation in >50% (actually 68-100%) of HCC cases examined in studies reported previously as genetic marker candidates for diagnosis of early HCC. [13][14][15][16][17][18][19][20][21] We then analyzed the methylation status of these genes in HCC and non-tumor liver tissues using sequencing and MSP, and evaluated their use, individually and in combination, as a diagnostic tool for the detection of early HCC.…”

RUNX3 protein is overexpressed in human basal cell carcinomas

“…More recently, we have demonstrated that RUNX3 is not detectable in 43 of 97 (44%) cases of gastric cancer, and a further 38% showed mislocalization in the cytoplasm, therefore suggesting that RUNX3 is inactivated in >80% of gastric cancers . Reduced expression of RUNX3 has now been observed in numerous human malignancies, including bladder (Kim et al, 2005), liver (Mori et al, 2005), colorectal (Ku et al, 2004) and lung cancers (Yanada et al, 2005). Furthermore, RUNX3 point mutations have been discovered in human gastric and bladder cancers (Li et al, 2002;Kim et al, 2005).…”