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RASSF1A Hypermethylation (rassf1a + hypermethylation)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Hypermethylation of RAS effector related genes and DNA methyltransferase 1 expression in endometrial carcinogenesis

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2008
Xiaoyun Liao
Abstract Epigenetic aberration is known to be important in human carcinogenesis. Promoter methylation status of RAS effector related genes, RASSF1A, RASSF2A, hDAB2IP (m2a and m2b regions) and BLU, was evaluated in 76 endometrial carcinomas and their non-neoplastic endometrial tissue by methylation specific PCR. Hypermethylation of at least one of the 5 genes was detected in 73.7% of carcinomas. There were significant correlations between methylation of hDAB2IP and RASSF1A, RASSF2A (p = 0.042, p = 0.012, respectively). Significantly, more frequent RASSF1A hypermethylation was found in Type I endometrioid carcinomas than Type II carcinomas (p = 0.049). Among endometrioid cancers, significant association between RASSF1A hypermethylation and advanced stage, as well as between methylation of hDAB2IP at m2a region with deep myometrial invasion (p < 0.05) was observed. mRNA expression of RASSF1A, RASSF2A and BLU in endometrial cancer cell lines significantly increased after treatment with the demethylating agent 5-Aza-2,-deoxycytidine supporting the repressive effect of hypermethylation on their transcription. Immunohistochemical study of DNMT1 on eight normal endometrium, 16 hyperplastic endometrium without atypia, 40 atypical complex hyperplasia and 79 endometrial carcinomas showed progressive increase in DNMT1 immunoreactivity from normal endometrium to endometrial hyperplasia and endometrioid carcinomas (p = 0.001). Among carcinomas, distinctly higher DNMT1 expression was observed in Type I endometrioid carcinomas (p < 0.001). DNMT1 immunoreactivity correlated with RASSF1A and RASSF2A methylation (p < 0.05). The data suggested that hypermethylation of RAS related genes, particularly RASSF1A, was involved in endometrial carcinogenesis with possible divergent patterns in different histological types. DNMT1 protein overexpression might contribute to such aberrant DNA hypermethylation of specific tumor suppressor genes in endometrial cancers. © 2008 Wiley-Liss, Inc. [source]

Comparison of DNA hypermethylation patterns in different types of uterine cancer: Cervical squamous cell carcinoma, cervical adenocarcinoma and endometrial adenocarcinoma

INTERNATIONAL JOURNAL OF CANCER, Issue 9 2006
Sokbom Kang
Abstract The incidence of cervical adenocarcinoma (CA) is rising, whereas the incidence of cervical squamous cell carcinoma (CSCC) continues to decrease. However, it is still unclear whether different molecular characteristics underlie these 2 types of cervical carcinoma. To better understand the epigenetic characteristics of cervical carcinoma, we investigated the DNA promoter hypermethylation profiles in CA and CSCC. In addition, we investigated whether DNA hypermethylation patterns might be used for the molecular diagnosis of CA and endometrial adenocarcinoma (EA). Using the bisulfite-modification technique and methylation-specific PCR, we examined the aberrant promoter hypermethylation patterns of 9 tumor suppressor genes (APC, DAPK, CDH1, HLTF, hMLH1, p16, RASSF1A, THBS1 and TIMP3) in 62 CSCCs, 30 CAs and 21 EAs. After Bonferroni correction adjustment (statistically significant at p < 0.0055), we found that the aberrant hypermethylations of CDH1 and DAPK were more frequent in CSCCs than in CAs (80.6% vs. 43.3%, p = 0.001; 77.4% vs. 46.7%, p = 0.005), whereas HLTF and TIMP3 were more frequently methylated in CAs (3.2% vs. 43.3%, p < 0.001; 8.1% vs. 53.3%, p = 0.001). The hypermethylations of RASSF1A and APC were more frequent in CAs than in CSCCs, but this was not significant (9.7% vs. 33.3%, p = 0.008; and 14.5% vs. 40.0%, respectively, p = 0.009). In addition, RASSF1A hypermethylation was significantly more frequent in EAs than in CAs (81.0% vs. 33.3%, p = 0.001). In conclusion, the existence of these unique methylation patterns in these cancers suggests that their tumorigenesis may involve different epigenetic mechanisms. © 2005 Wiley-Liss, Inc. [source]

Combined BubR1 protein down-regulation and RASSF1A hypermethylation in Wilms tumors with diverse cytogenetic changes

MOLECULAR CARCINOGENESIS, Issue 9 2008
Masayuki Haruta
Abstract BUB1B and RASSF1A genes play specific roles in the mitotic checkpoint, and their defects may cause chromosome instability or aneuploidy in mouse fibroblasts and human cancer cell lines; however, few studies have reported a correlation between defects in these genes and chromosome changes in human tumor samples. We examined chromosome abnormalities in 25 Wilms tumors by metaphase comparative genomic hybridization, and classified them into 14 hyperdiploid (50,,,chromosomes), 2 near-or-pseudodiploid, and 9 diploid tumors. We also examined various molecular aspects of BUB1B and RASSF1A, and evaluated the relationship between chromosome changes and the status of both genes. No tumors showed BUB1B mutation. BubR1 protein (BUB1B gene product) expression was undetectable or decreased in five of six hyperdiploid or near-or-pseudodiploid tumors and increased in four of five diploid tumors, whereas all seven tumors examined showed BUB1B mRNA expression irrespective of their chromosome pattern. Furthermore, while complete promoter methylation of RASSF1A was found in 13 of 16 hyperdiploid or near-or-pseudodiploid tumors, unmethylated RASSF1A was found in 5 of 9 diploid tumors. Partial RASSF1A methylation was found in three hyperdiploid or near-or-pseudodiploid tumors and in four diploid tumors. Thus, BubR1 protein expression decreased, and the promoter region of RASSF1A was completely methylated in the great majority of hyperdiploid or near-or-pseudodiploid tumors, BubR1 protein expression increased and RASSF1A was unmethylated in the majority of diploid tumors. These findings suggest that the combined BubR1 protein down-regulation and RASSF1A hypermethylation might be implicated in the formation of chromosomal changes found in Wilms tumors. © 2008 Wiley-Liss, Inc. [source]