Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Promoter hypermethylation is an important pathway for the repression of gene transcription in cancer. We investigated promoter hypermethylation of six genes, p16, APC, HIC-1, death-associated protein kinase (DAPK), O(6)-methylguanine-DNA-methyltransferase (MGMT), and E-cadherin, in uterine cervical carcinoma from 53 patients including 31 cases of squamous cell carcinoma (SCC) and 22 cases of adenocarcinoma (AC). Aberrant methylation of at least one of these genes was detected in 79% (42 of 53) of cases including 71% (22 of 31) of SCC and 91% (20 of 22) of AC cases. No aberrant methylation was detected in normal cervical tissue from 24 control hysterectomy specimens. There was no correlation between promoter hypermethylation at any gene and the presence of human papillomavirus-16 or -18 E7 DNA. In AC cases, promoter hypermethylation of the APC and HIC-1 genes was detected at a statistically significant higher frequency than in the SCC cases (APC, 60% versus 13%, P < 0.001; HIC-1, 63% versus 32%, P < 0.03). Conversely, promoter hypermethylation of p16 and DAPK was more common in SCC cases than in AC cases. Our results suggest that promoter hypermethylation is a frequent epigenetic event in cervical carcinoma. The pattern of gene promoter hypermethylation is distinctly different between AC and SCC. The absence of these epigenetic alterations in normal cervical tissue suggests that they may also be valuable as cancer markers.
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PMID:Promoter hypermethylation of multiple genes in carcinoma of the uterine cervix. 1144 14

Serrated adenoma is a recently described entity characterized by having combined architectural features of hyperplastic polyps and classical adenoma. To understand the role of gene regulation in the progression of the serrated neoplasia pathway, we examined the methylation profiles of the promoter regions of 19 genes, DNA ploidy, and mutator phenotype status. In all, 40 sporadic, classical serrated adenomas were pathologically reviewed and divided into four pathologic groups according to their histologic grades. Methylation-specific PCR was performed using primers for p16, hMLH1, RASSF1A, APC, HIC-1, DAPK, MGMT, SLC5A8, RB1, H-Cadherin, E-Cadherin, TIMP3, PTEN, THBS1, LKB1, p14, p15, FHIT, and VHL. Dual flow-cytometric analyses using cytokeratin and DAPI and MSI studies using BAT26 were also performed. Methylation was observed in 2.5-82.5% (mean 33.9%) of the CpG islands in the promoter regions of 16 genes. The tumors with higher histologic grades, including carcinomas, showed more extensive methylation compared to those with lower grades, and serrated adenomas in the right colon showed more frequent methylation than those in the left (P<0.05). Tumor-specific promoter methylation of SLC5A8 was observed in 33 (82.5%) of the serrated adenomas. Aneuploidization with near-diploid DNA indices was detected in four out of 28 cases examined (14.3%); two were low-grade serrated adenomas and two were carcinomas in the left colon. The high mutator phenotype was not observed in any of the cases examined. Our results indicate that: (1) aberrant, widespread methylation of CpG islands increases with the histological progression of serrated adenomas; (2) methylation of SLC5A8 is an early event; and (3) additional methylation of the p16, p14, MGMT, TIMP3, and FHIT genes are important tumorigenic steps in the serrated neoplasia pathway.
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PMID:Progressive methylation during the serrated neoplasia pathway of the colorectum. 1538 52

DNA methylation is a promising biomarker for cancer. This study was aimed at investigating the methylation levels of multiple genes in hepatocellular carcinoma (HCC) and to identify a combination of methylation markers that would be useful for the diagnosis of HCC. The methylation status of a panel of nine tumor-associated genes (APC, GSTP1, RASSF1A, CDKN2A, SFRP1, RUNX3, SOCS1, Hint1, and HIC-1) in 8 normal liver tissues and 47 paired HCCs and non-tumorous tissues (NTs) was determined using a modified methylation-sensitive, restriction enzyme-based quantitative PCR (MSRE-qPCR) method. The methylation levels of six genes (APC, CDKN2A, GSTP1, RASSF1A, SFRP1 and RUNX3) were significantly higher in HCCs than in adjacent NTs (P<0.05). Although the AUC (area under the curve) for each individual gene was low to moderate (range: 0.576 to 0.835) according to receiver operator characteristic (ROC) curve analysis, the combination analysis of these six genes resulted in an increase of AUC of 0.954 with 85.1% sensitivity, 89.4% specificity, 88.9% positive predictive value, and 85.7% negative predictive value in discriminating HCC tissues from NT tissues. These results indicate that the analysis of a combination of these six methylated genes may be a promising method for the risk assessment and diagnosis of HCC.
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PMID:Quantitative methylation analysis of multiple genes using methylation-sensitive restriction enzyme-based quantitative PCR for the detection of hepatocellular carcinoma. 2160 Feb 1