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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aberrant promoter methylation of CpG islands of tumor suppressor genes inhibits expression of the genes and may lead to tumorigenesis. We investigated the aberrant methylation profile of potential tumor suppressor genes of p15, p16, SOCS-1, and Wnt signaling pathway in colorectal cancers and correlated the data with clinical findings. Cancerous and nearby non-cancerous tissues of 185 sporadic colorectal cancer samples were studied. Methylation specific PCR was performed to explore the mechanism of inactivation in p15, p16, SOCS-1, E-cadherin, APC, GSK-3beta, and Axin1 genes. Aberrant promoter methylation in p15, p16, SOCS-1, E-cadherin, APC, GSK-3beta, and Axin1 genes were 5.9, 7.0, 3.8, 5.9, 12.4, 2.2, and 0% for cancerous tissues, respectively, whereas the frequencies were 3.8, 0, 0, 7.0, 2.7, 0.5, and 0% for nearby non-cancerous tissues, respectively. The frequency of aberrant promoter methylation of cancerous tissues was significant higher than non-cancerous tissues in p16, SOCS-1, and APC genes (p<0.05) and methylation status of these genes had no clear relationship with clinical parameters. Of the 66 patients who showed at least one aberrant promoter methylation in the tumor-suppressor genes, 5 (7.6%) patients demonstrated multiple methylation phenotype (methylation > or =3) and associated with increased lymph node metastasis (p=0.036). Our findings suggest that inactivation of some tumor suppressor genes through aberrant promoter methylation of CpG islands may play a role in the development of colorectal cancer and methylation inactivation of these genes except p16 and SOCS1 may occur at the precancerous stage. Multiple methylation pathways may be involved in the tumorigenesis of colorectal cancer and associated with aggressiveness of clinical disease.
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PMID:Promoter CpG methylation of tumor suppressor genes in colorectal cancer and its relationship to clinical features. 1471 65

Urothelial carcinomas (TCC) constitute the vast majority of bladder cancers in most of the world. On the other hand, squamous cell bladder carcinoma, a rare subtype in the Western world, is a common subtype in areas with endemic Schistosoma infection. Although schistosomal infection has been reported to influence DNA methylation, the pattern and extent of CpG island hypermethylation in squamous cell carcinomas remain unknown. In this study, we used methylation-specific PCR to characterize 12 cancer-related genes in 41 bladder cancer samples from Egypt (31 squamous cell carcinomas (SCC), 21 of them associated with Schistosoma and 10 TCC, five of which were Schistosoma-associated). The genes analyzed included E-cadherin, DAP-Kinase, O6MGMT, p14, p15, p16, FHIT, APC, RASSF1A, GSTP1, RARbeta and p73. Methylation of at least one gene was detected in all squamous cell tumors except two, and 45% of samples had at least three methylated genes. The average methylation index was 0.24, corresponding to three of the 12 analyzed genes. Schistosoma-associated tumors had more genes methylated than non-Schistosoma tumors (average MI: 0.29 vs 0.14) (P = 0.027). Although the extent of methylation in TCC (average MI: 0.16) was lower than in squamous cell carcinomas (SCC), the overall profile of methylation was similar, with Schistosoma-associated cases having a higher methylation index. Our results suggest that schistosomal involvement associates with a greater degree of epigenetic changes in the bladder epithelium.
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PMID:CpG island methylation in Schistosoma- and non-Schistosoma-associated bladder cancer. 1515 12

Methylation profile was analyzed in nine cases of relapsed childhood acute lymphoblastic leukemia (ALL) for p14, p15, p16, Rb, MGMT, APC, hMLH1, RARbeta, RIZ, DAPK, and FHIT genes by using methylation specific polymerase chain reaction (MSP) analysis. Frequency of methylation in each gene was: MGMT, 56%; RARbeta, 44%; and p16, 22%, respectively. None of the p14, p15, Rb, APC, hMLH1, RIZ, DAPK, and FHIT genes were hypermethylated. Five (56%) of 9 cases showed methylation of at least one gene. All of the samples with hypermethylation in p16 and MGMT gene at relapse, had already acquired the change at the time of initial diagnosis. Interestingly, three of 4 cases with RARbeta gene methylation at relapse did not have methylation of this gene at the time of initial presentation. These results suggest that hypermethylation might be involved in the relapse of childhood ALL.
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PMID:Aberrant methylation in promoter-associated CpG islands of multiple genes in relapsed childhood acute lymphoblastic leukemia. 1520 66

Gene promoter hypermethylation is increasingly recognized to play an important role in cancer development through silencing of gene transcription. This study determined the methylation profiles of primary colorectal cancers and adenomas to elucidate the role of epigenetic changes in different stages of colorectal carcinogenesis. We examined the methylation profiles of 47 sporadic colorectal cancers, 36 colonic adenomas from patients without cancer and 34 colonic biopsies from patients without colonic lesions. Paired adjacent dysplasia tissues obtained from 17 cancer patients were also examined. Promoter hypermethylation in 10 tumor-related genes (APC, ATM, GSTP1, HLTF, MGMT, hMLH1, p14, p15, SOCS-1 and TIMP-3) were studied by methylation-specific PCR. Promoter hypermethylation was frequently detected in more than 40% of colonic cancers and adenomas in APC, ATM, HLTF, MGMT and hMLH1 genes (p < 0.0001 vs. normal). While low level of methylation was detected in p14, p15 and TIMP-3, there was no methylation detected in GSTP1 and SOCS-1. The frequencies of methylation were comparable between tumors and adenomas, and advanced and nonadvanced adenoma. In contrast, K-ras mutation was only detected in advanced adenomas and cancers. Concurrent methylation in >/= 3 genes was found in 66.7% adenomas and 68.1% cancers but not in normal colonic tissues. Methylation was associated with reduced protein expressions in colorectal adenomas and cancers. Moreover, methylation in ATM was more common in older cancer patients (p = 0.002), but there was no significant association between promoter hypermethylation and other clinicopathologic characteristics of cancer. Our study demonstrated the early and specific involvement of promoter hypermethylation in the colorectal adenoma-carcinoma sequence.
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PMID:Promoter hypermethylation of tumor-related genes in the progression of colorectal neoplasia. 1538 72

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

While genetic factors clearly play a key role in colorectal cancer (CRC) pathogenesis and in determining its phenotypic features, the precise genes that involved are largely unknown. To gain insight into these genes, consecutive Israeli CRC patients were genotyped using SNPs from within candidate genes: APC, beta-Catenin, K-RAS, DCC, P16, PTEN, RB1, P15, APOE, ERCC2, P53, MTHFR and hMSH2. Genotyping of consecutive, unselected colorectal cancer patients was done mostly by utilizing the MassARRAY technology (Sequenom) and to a lesser extent DGGE, ARMS and direct DNA sequencing. Correlation of genotypes with specific phenotypic features was carried out for all patients and separately for the Ashkenazim. Overall, 456 patients were analyzed, the majority (64.25%) being of Ashkenazi origin; mean age at diagnosis was 65.6 +/- 14 (range 25-90 years), and the mean follow-up was 4.7 +/- 0.28 (range 0-30 years). Statistically significant associations were noted between SNPs in beta-catenin and APOE and a positive family history of cancer (beta-catenin: p=0.034, APOE: p=0.033); tumor location and a DCC SNP (p=0.038) and the P53 R72P mutation and survival (p=0.0336). In Ashkenazi patients, ERCC2 and MTHFR genes' SNPs were associated with age at diagnosis (ERCC2: p=0.025, MTHFR: p=0.0005); a P53 polymorphism, APOE and Rb SNPs with a family history of cancer (P53 p=0.034;APOE p=0.04, Rb p= 0.022); DCC SNP with tumor location (p=0.014); and p15 SNP with tumor grade (p=0.032). This preliminary study shows that genetic factors play a role in determining CRC phenotypic features and that a larger cohort with longer follow-up is clearly needed.
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PMID:Genotype phenotype correlations in Israeli colorectal cancer patients. 1552 94

Promoter hypermethylation represents a primary mechanism in the inactivation of tumor suppressor genes during tumorigenesis. We analyzed the promoter methylation status of eight tumor-associated genes (p14 ARF, p15 INK4B, p16 INK4A, Rb, hMLH1, hMSH2, APC, and DAPK) in 30 patients with myelofibrosis with myeloid metaplasia (MMM) by methylation specific PCR. The study showed no hypermethylation of the promoters of p16(INK4A), Rb, hMLH1, hMSH2, APC, and DAPK genes. The p14 ARF, p15 INK4B promoters were hypermethylated in only one patient each. This study indicates that, although methylation of these genes is important in other cancers, it is rare in MMM and causation of this disease should be focused elsewhere.
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PMID:Methylation analysis of the cell cycle control genes in myelofibrosis with myeloid metaplasia. 1575 3

While there is no reliable serum biomarker for the diagnosis and monitoring of patients with gastric cancer, we tested the potential diagnostic and prognostic values of detecting methylation changes in the serum of gastric cancer patients. DNA was extracted from the pretherapeutic serum of 60 patients with confirmed gastric adenocarcinoma and 22 age-matched noncancer controls. Promoter hypermethylation in 10 tumour-related genes (APC, E-cadherin, GSTP1, hMLH1, MGMT, p15, p16, SOCS1, TIMP3 and TGF-beta RII) was determined by quantitative methylation-specific PCR (MethyLight). Preferential methylation in the serum DNA of gastric cancer patients was noted in APC (17%), E-cadherin (13%), hMLH1 (41%) and TIMP3 (17%) genes. Moreover, patients with stages III/IV diseases tended to have higher concentrations of methylated APC (P = 0.08), TIMP3 (P = 0.005) and hMLH1 (P = 0.03) in the serum. In all, 33 cancers (55%) had methylation detected in the serum in at least one of these four markers, while three normal subjects had methylation detected in the serum (specificity 86%). The combined use of APC and E-cadherin methylation markers identified a subgroup of cancer patients with worse prognosis (median survival 3.3 vs 16.1 months, P = 0.006). These results suggest that the detection of DNA methylation in the serum may carry both diagnostic and therapeutic values in gastric cancer patients.
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PMID:Potential diagnostic and prognostic values of detecting promoter hypermethylation in the serum of patients with gastric cancer. 1594 35

Chromosome abnormalities of 6q are not frequently observed in myeloid disorders. In this article, we report the incidence of these chromosome changes in childhood myeloid leukemia as 2%-4% based on the cytogenetic database of a single institution. We applied fluorescence in situ hybridization (FISH) to characterize precisely the types of 6q abnormalities in seven patients (six with acute myeloid leukemia and one with myelodysplastic syndrome). They carried various translocations involving different breakpoints in 6q, as confirmed by FISH using a whole-chromosome-6 paint. Four cases were reported as t(6;11), although the breakpoints varied. Among these, we identified a novel translocation, t(6;11)(q24.1;p15.5), in a patient with acute megakaryoblastic leukemia. Molecular cytogenetic studies using the PAC clone RP5-1173K1 localized the genomic breakpoint on chromosome 11 to within the NUP98 gene. The breakpoint on chromosome 6 was narrowed down to a 500-kb region between BAC clones RP11-721P14 and RP11-39H10. Reverse-transcription PCR was performed using a forward primer specific for NUP98 and a reverse primer for the candidate gene in the 500-kb interval in 6q. This experiment resulted in the identification of a new fusion between NUP98 and C6orf80. Further studies will aim to fully characterize C6orf80 and will elucidate the role of this new NUP98 fusion in myeloid leukemia.
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PMID:Characterization of 6q abnormalities in childhood acute myeloid leukemia and identification of a novel t(6;11)(q24.1;p15.5) resulting in a NUP98-C6orf80 fusion in a case of acute megakaryoblastic leukemia. 1602 18

Methylation profile was analyzed in 10 childhood acute lymphoblastic leukemia (ALL) and nine adult ALL cases. Four genes (p15, p16, RARbeta, FHIT) had methylation in both diseases, four genes (p14, Rb, MLH1, DAPK) showed no methylation in both diseases, and the two genes (APC, RIZ) demonstrated methylation only in adult ALL. Methylation of the RARbeta was more frequent in adult ALL than that in childhood ALL (p=0.01). The number of patients with methylation of multiple genes was higher in adult ALL than that in childhood ALL (p=0.006). Moreover, overall frequency of methylation was higher in adult ALL than that in childhood ALL (p=0.01).
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PMID:Aberrant methylation in promoter-associated CpG islands of multiple genes in acute lymphoblastic leukemia. 1603 15


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