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Runx3/Pebp2alphaC null mouse gastric mucosa exhibits hyperplasias due to stimulated proliferation and suppressed apoptosis in epithelial cells, and the cells are resistant to growth-inhibitory and apoptosis-inducing action of TGF-beta, indicating that Runx3 is a major growth regulator of gastric epithelial cells. Between 45% and 60% of human gastric cancer(More)
A subset of colorectal cancer shows significant accumulation of aberrant promoter methylation. Previously, we developed two groups of methylation markers that classified colorectal cancer into three epigenotypes: i) high-, ii) intermediate-, and iii) low-methylation epigenotypes. High-methylation epigenotype, with methylation of both group 1 and group 2(More)
INTRODUCTION Risk prediction of gastric cancers is important to implement appropriate screening procedures. Although aberrant DNA methylation is deeply involved in gastric carcinogenesis, its induction by Helicobacter pylori, a strong gastric carcinogen, is unclear. Here, we analyzed the effect of H. pylori infection on the quantity of methylated DNA(More)
A subgroup of colorectal cancer (CRC) shows non-random accumulation of aberrant DNA methylation, so-called CpG island methylator phenotype (CIMP), which was associated with microsatellite instability and BRAF mutation. As just one group of methylation markers was suitable to extract CIMP+/CIMP-high, and had been commonly used in the "one-panel method", it(More)
Epigenetic alterations in cancer occur at least as commonly as genetic mutations, but epigenetic alterations could occur secondarily to the tumor process itself. To establish a causal role of epigenetic changes, investigators have turned to genetically engineered mouse models. Here, we review a recent study showing that a mouse model of loss of imprinting(More)
Neuroblastoma, one of the most common pediatric solid tumors, is characterized by two extreme disease courses, spontaneous regression and life-threatening progression. Here, we conducted a genome-wide search for differences in DNA methylation that distinguish between neuroblastomas of the two types. Three CpG islands (CGI) and two groups of CGIs were found(More)
Epstein-Barr virus (EBV) establishes latent infection and is associated with tumors, such as Burkitt lymphoma, nasopharyngeal carcinoma, and gastric cancers. We recently reported that EBV(+) gastric cancer shows an EBV(+)/extensively high-methylation epigenotype, and in vitro EBV infection induces extensive DNA methylation with gene repression within 18(More)
Aberrantly methylated DNA fragments in a human gastric cancer were searched for by a genome-scanning method, methylation-sensitive-representational difference analysis (MS-RDA). Six DNA fragments flanked by CpG islands (CGIs) and hypermethylated in the cancer were isolated. Four of the 6 fragments possessed genes in their vicinities. Quantitative RT-PCR(More)
Despite the recent advances in the therapeutic modalities, colorectal cancer (CRC) remains to be one of the most common causes of cancer-related death. CRC arises through accumulation of multiple genetic and epigenetic alterations that transform normal colonic epithelium into adenocarcinomas. Among crucial roles of epigenetic alterations, gene silencing by(More)
Loss of imprinting (LOI) of the insulin-like growth factor II gene (IGF2) is an epigenetic alteration that results in a modest increase in IGF2 expression, and it is present in the normal colonic mucosa of about 30% of patients with colorectal cancer. To investigate its role in intestinal tumorigenesis, we created a mouse model of Igf2 LOI by crossing(More)