Hypermethylation of the hMLH1 gene promoter in solitary and multiple gastric cancers with microsatellite instability

Sakata, Ken; Tamura, Gen; Endoh, Yasushi; Ohmura, Kiyonari; Ogata, Shinya; Motoyama, Teiichi

doi:10.1038/sj.bjc.6600076

Cited by 39 publications

(34 citation statements)

References 26 publications

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“…Prolactin expression and growth of salt-challenged tilapia are associated with the presence of a microsatellite in the promoter region of that gene (Streelman and Kocher, 2002). Microsatellites in promoter regions are also associated with the development of cancer (Deng et al, 2002;Sakata et al, 2002;Stefansson et al, 2002), with gene expression in bacteria (Liu et al, 2002) and with germination control in plants (Carrari et al, 2001). On the other hand, there are several reports of evidence that QTLs in this region of BTA 5 affect rib bone and dressing percentage in Brahman X Hereford sire progenies (Stone et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Association of GH and IGF-1 polymorphisms with growth traits in a synthetic beef cattle breed

et al. 2005

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The Canchim beef cattle (5/8 Charolais + 3/8 Zebu) has been selected for meat production in Brazil since late 1950. In the present work the effects of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) polymorphisms were investigated in 688 animals born between 1998 and 2000. These animals belonged to two genetic groups, i.e., traditional and new lineages. Genotype effects on expected breeding values for birth weight (BW), weaning weight (WW) and yearling weight (YW) were investigated by the least square method. Significant effects were found for GH genotype on YW (p ≤ 0.05), with positive effects associated with the LV (leucine/valine) genotype. For IGF-1 genotypes, significant effects were found on BW (p ≤ 0.01) and YW (p ≤ 0.01). Average substitution effects for IGF-1 alleles estimated by regression analysis suggested a positive effect of the IGF-1 225 bp allele on BW and of the 229 bp allele on YW.

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Section: Discussionmentioning

confidence: 99%

Association of GH and IGF-1 polymorphisms with growth traits in a synthetic beef cattle breed

et al. 2005

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“…Previously, we and others reported similar finding for p16, hMLH1, TSLC1 and hDAB2IP, implying that the methylation of several TSGs and tumor-related genes appears to be an important mechanism in the tumorigenesis of GC arising from the antrum. [43][44][45][46] Because intestinal metaplasia commonly arises in the antrum and then extends towards the body of the stomach, intestinal metaplasia may predispose these genes to DNA methylation. 47 We previously reported the geographic differences in the methylation profiles of lung cancers.…”

Section: Discussionmentioning

confidence: 99%

Aberrant promoter methylation of insulin‐like growth factor binding protein‐3 gene in human cancers

Tomii

Tsukuda

Toyooka

et al. 2006

Intl Journal of Cancer

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Insulin-like growth factor binding protein-3 (IGFBP-3) is postulated to be a mediator of growth suppression signals. Here, we examined the methylation status of IGFBP-3 to correlate to clinicopathological factors in human cancers. The methylation status of IGFBP-3 was determined by bisulfite DNA sequencing and was correlated with expression semi-quantified by real-time RT-PCR to develop a methylation-specific PCR (MSP) assay for IGFBP-3. Using the MSP assay, we examined the methylation status of IGFBP-3 in gastric cancer (GC), colorectal cancer (CRC), breast cancer (BC) and malignant mesothelioma (MM). IGFBP-3 methylation was detected in 6 of 13 (46%) and 16 of 24 (67%) GC cell lines and tumors, respectively; 4 of 8 (50%) and 15 of 26 (58%) CRC cell lines and tumors, respectively; 3 of 11 (27%) and 7 of 39 (18%) BC cell lines and tumors, respectively and 1 of 5 (20%) and 18 of 56 (32%) MM cell lines and tumors, respectively. Interestingly, the methylation status of MM specimens from Japanese patients (75%, 12 out of 16 patients) was significantly higher than those from the USA (15%, 6 out of 40 patients) (p < 0.0001), suggesting the presence of ethnic differences in the IGFBP-3 methylation status. We also found that IGFBP-3 methylation was preferentially present in GCs arising in the lower-third of the stomach (p 5 0.079). In summary, our results showed that IGFBP-3 methylation played an important role in the silencing of its expression, suggesting that IGFBP-3 may act as a tumor suppressor gene in several human cancers examined. ' 2006 Wiley-Liss, Inc.

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“…So far, numerous examples of aberrant CpG island promoter hypermethylation have been observed in tumor-suppressor genes, genes involved in cell-cell adhesion, and genes that play an important role in DNA repair [28]. Aberrant methylation of tumor-suppressor genes has also been observed in normal tissues adjacent to tumors in cases of OSCC, HCC, HNSCC, and gastric cancers [22,[29][30][31][32]. In all studies, the incidence of hypermethylation was higher in tumor tissues than in the corresponding adjacent normal tissues, suggesting that aberrant DNA methylation is an early event of carcinogenesis, including hepatocarcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…We also investigated the promoter methylation status of hMLH1. Silencing hMLH1 has been detected in different tumors [17,32,39,[41][42][43][49][50][51]. However, hMLH1 promoter methylation was not detected in sporadic renal cell carcinoma (RCC) and multiple myeloma (MM) [52,53].…”

Section: Acknowledgmentsmentioning

confidence: 99%

Correlation of chromosome damage and promoter methylation status of the DNA repair genes MGMT and hMLH1 in Chinese vinyl chloride monomer (VCM)-exposed workers

Wu¹,

Liu²,

Qiu³

et al. 2013

International Journal of Occupational Medicine and Environmental Health

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Objective: To explore the association of the methylation status of MGMT and hMLH1 with chromosome damage induced by vinyl chloride monomer (VCM). Materials and Methods: Methylation of MGMT and hMLH1 was measured in 101 VCM-exposed workers by methylation-specific PCR. Chromosome damage in peripheral blood lymphocytes was measured by the cytokinesis-block micronucleus assay. The subjects were divided into chromosome damaged and non-damaged groups based on the normal reference value of micronuclei frequencies determined for two control groups. Results: MGMT promoter methylation was detectable in 5 out of 49 chromosome damaged subjects, but not in the chromosome non-damaged subjects; there was a significant difference in MGMT methylation between the two groups (p < 0.05). Conclusions: We detected aberrant promoter methylation of MGMT in a small number of chromosome damaged VCM-exposed workers, but not in the chromosome non-damaged subjects. This preliminary observation warrants further investigation in a larger study. inactivation of tumor suppressor genes in human cancers. Several investigators have reported that CpG islands on the promoters of the MGMT and hMLH1 genes are hypermethylated in several malignancies and aberrant hypermethylation represses the expression of MGMT and hMLH1 [17][18][19][20]. A high frequency of p16 hypermethylationin was observed in vinyl chloride (VC)-associated hepatocellular carcinomas (HCC) [21]. Aberrant methylation of tumor suppressor genes might also act in the early stages of the multistep process of carcinogenesis [22]. Based on the information above, we hypothesized that epigenetic silencing of MGMT and hMLH1, by promoter hypermethylation, might be involved in VCM-exposureinduced chromosome damage which is the early stage in the process of liver angiosarcoma. In the present study, we attempted to identify the MGMT and hMLH1 promoter methylation status in genomic DNA isolated from peripheral blood lymphocytes from workers exposed to VCM using a methylation-specific polymerase chain reaction (MS-PCR) and to analyze the correlation between MGMT and hMLH1 gene promoter methylation and chromosome damage induced by VCM exposure. MATERIALS AND METHODS Study populationWorkers employed in a VCM polymerization plant in China were studied. Prior to the study, written informed consent had been obtained from each subject and a standardized questionnaire had been used to obtain personal information, smoking and alcohol habits, medication and occupational history. The subjects exposed to VCM for longer than one year were selected if the following criteria were met: detailed questionnaires had been completed, the CBMN test results and a blood sample had been provided and the MSP analysis for the MGMT and hMLH1 genes was completed successfully. A total of 101 workers met these criteria. Individuals who smoked once a day for

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Hypermethylation of the hMLH1 gene promoter in solitary and multiple gastric cancers with microsatellite instability

Cited by 39 publications

References 26 publications

Association of GH and IGF-1 polymorphisms with growth traits in a synthetic beef cattle breed

Association of GH and IGF-1 polymorphisms with growth traits in a synthetic beef cattle breed

Aberrant promoter methylation of insulin‐like growth factor binding protein‐3 gene in human cancers

Correlation of chromosome damage and promoter methylation status of the DNA repair genes MGMT and hMLH1 in Chinese vinyl chloride monomer (VCM)-exposed workers

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