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RASSF1A Genes (rassf1a + gene)
Selected AbstractsMethylation profile in tumor and sputum samples of lung cancer patients detected by spiral computed tomography: A nested case,control studyINTERNATIONAL JOURNAL OF CANCER, Issue 5 2006Rosalia Cirincione Abstract We evaluated the aberrant promoter methylation profile of a panel of 3 genes in DNA from tumor and sputum samples, in view of a complementary approach to spiral computed tomography (CT) for early diagnosis of lung cancer. The aberrant promoter methylation of RAR,2, p16INK4A and RASSF1A genes was evaluated by methylation-specific PCR in tumor samples of 29 CT-detected lung cancer patients, of which 18 had tumor-sputum pairs available for the analysis, and in the sputum samples from 112 cancer-free heavy smokers enrolled in a spiral CT trial. In tumor samples from 29 spiral CT-detected patients, promoter hypermethylation was identified in 19/29 (65.5%) cases for RAR,2, 12/29 (41.4%) for p16INK4A and 15/29 (51.7%) for RASSF1A. Twenty-three of twenty-nine (79.3%) samples of the tumors exhibited methylation in at least 1 gene. In the sputum samples of 18 patients, methylation was detected in 8/18 (44.4%) for RAR,2 and 1/18 (5%) for both RASSF1A and p16INK4A. At least 1 gene was methylated in 9/18 (50%) sputum samples. Promoter hypermethylation in sputum from 112 cancer-free smokers was observed in 58/112 (51.7%) for RAR,2 and 20/112 (17.8%) for p16, whereas methylation of the RASSF1A gene was found in only 1/112 (0.9%) sputum sample. Our study indicates that a high frequency of hypermethylation for RAR,2, p16INK4A and RASSF1A promoters is present in spiral CT-detected tumors, whereas promoter hypermethylation of this panel of genes in uninduced sputum has a limited diagnostic value in early lung cancer detection. © 2005 Wiley-Liss, Inc. [source] Combined BubR1 protein down-regulation and RASSF1A hypermethylation in Wilms tumors with diverse cytogenetic changesMOLECULAR CARCINOGENESIS, Issue 9 2008Masayuki 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] Reduced expression of the Rassf1a gene and its aberrant DNA methylation in pancreatic duct adenocarcinomas induced by N-nitrosobis(2-oxopropyl)amine in hamstersMOLECULAR CARCINOGENESIS, Issue 2 2008Kyoko Shimizu Abstract Alterations of the Rassf1a gene were investigated in pancreatic duct adenocarcinomas (PDAs) induced by N-nitrosobis(2-oxopropyl)amine (BOP) in hamsters. Female Syrian golden hamsters received 70 mg/kg BOP, followed by repeated exposures to an augmentation pressure regimen consisting of a choline-deficient diet combined with a sequential course of DL -ethionine, L -methionine, and 20 mg/kg BOP. A total of 15 PDAs were obtained, and total RNAs were assessed by real-time quantitative reverse transcription (RT)-polymerase chain reaction (PCR). Expression of the Rassf1a was significantly reduced in PDAs (P,<,0.005) compared with normal pancreatic tissues. For analysis of methylation status, bisulfite sequencing was performed. Normal tissues were all unmethylated in the 5, upstream region of Rassf1a. In contrast, four PDAs were highly methylated, correlating with reduced expression of the Rassf1a gene. Using reverse transcription (RT)-polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis, mutations were detected in 3 out of 15 PDAs (20%). These results suggested that alterations of the Rassf1a gene may be involved in development of PDAs induced by BOP in hamsters. © 2007 Wiley-Liss, Inc. [source] | ||||||||||