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Malyukova A. V. Loginov W. I. Hodyrev D. S. Kadyrova E. L. Pronina I. V. Ivanova T. A. Kisseljov F. L. Zabarovsky E. R. Kisseljova N. P. Braga E. A. 《Molecular Biology》2004,38(6):857-864
Methylation-sensitive restriction endonuclease analysis (MSRA) followed by polymerase chain reaction (PCR) have been used to estimate the methylation level of 13 CpG dinucleotides in the promoter region of the putative suppressor gene RASSF1A (3p21.31) in squamous cell carcinomas of the uterine cervix (SCCs) carrying human papillomavirus (HPV) types 16, 18, and related types. Methylation of 3 to 13 CpG pairs has been found in 64% (25 out of 39) tumor DNA samples, 22% (2 out of 9) DNA samples from morphologically normal tissues adjacent to the tumor (P = 0.0306), and two out of three DNA samples from peripheral blood leukocytes of carcinoma patients. These CpG pairs are not methylated in the DNA of leukocytes of healthy donors (0 out of 10). The methylation level of the RASSF1A promoter region studied in tumors of the patients with regional lymph node metastases is significantly higher than in tumors of the patient that have no metastases (P = 8.5 × 10–12). The methylation frequency of gene RASSF1A is two times higher than the frequency of hemi- and homozygous deletions in the chromosome 3 region where the gene is located. The data obtained indicate that methylation is one of the main mechanisms of the RASSF1A gene inactivation in HPV-positive human cervical tumors. The methylation of this gene may be an early event in the genesis of cervical tumors, the methylation level increasing with tumor progression. 相似文献
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Viera Kajabova Bozena Smolkova Iveta Zmetakova Katarina Sebova Tomas Krivulcik Vladimir Bella Karol Kajo Katarina Machalekova Ivana Fridrichova 《Translational oncology》2013,6(3):297-IN5
The aim of this study was to investigate the relationship between the promoter methylation in five cancer-associated genes and clinicopathologic features for identification of molecular markers of tumor metastatic potential and hormone therapy response efficiency in breast cancer. The methylation levels in paraffin-embedded tumor tissues, plasma, and blood cells from 151 sporadic breast cancer patients and blood samples of 50 controls were evaluated by quantitative multiplex methylation-specific polymerase chain reaction. DNA methylation of RAS-association domain family member 1 (RASSF1A), estrogen receptor 1 (ESR1), cadherin 1, type 1, E-cadherin (CDH1), TIMP metallopeptidase inhibitor 3 (TIMP3) and spleen tyrosine kinase (SYK) genes was detected in the tumors of 124, 19, 15, 15, and 6 patients with mean levels of 48.45%, 3.81%, 2.36%, 27.55%, and 10.81%, respectively. Plasma samples exhibited methylation in the same genes in 25, 10, 15, 17, and 3 patients with levels of 22.54%, 17.20%, 22.87%, 31.93%, and 27.42%, respectively. Cumulative methylation results confirmed different spectra in tumor and plasma samples. Simultaneous methylation in tumors and plasma were shown in less than 17% of patients. RASSF1A methylation levels in tumor samples statistically differ according to tumor size (P = .029), estrogen receptor (ER) and progesterone receptor (PR) status (P = .000 and P = .004), and immunohistochemical subtype (P = .000). Moreover, the positive correlation was found between RASSF1A methylation levels and percentage of cancer cells expressing ER and PR. The direct relationship between RASSF1A promoter methylation and expression of ER could aid the prognosis of hormonal therapy response. 相似文献
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K. Fabianowska-Majewska R. Kordek B. Krawczyk 《Nucleosides, nucleotides & nucleic acids》2013,32(9-11):1025-1028
In the tested samples of sporadic breast cancer (100 cases), hypermethylation of CpG sequences located in ERα promoter was observed in 62 cases. It correlated with: (i) deficiency of ERα protein in 45%, (ii) hypermethylation of BRCA1 promoter in 95%, and (iii) nonmethylated E-cadherin promoter in 90%. Fifty-eight percent of the patients with nonmethylated E-cadherin promoter (56 cases) did not show metastasis to lymphatic nodes. The analysis of the methylation level of the promoter of ERα, BRCA1, and E-cadherin, frequently connected with their activity, shows that it can be an important parameter in the diagnosis and therapeutic strategies in sporadic breast cancer. 相似文献
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Zemlyakova V. V. Zhevlova A. I. Strelnikov V. V. Lyubchenko L. N. Schabanov M. A. Vishnevskaya Ya. V. Tretyakova V. A. Zaletayev D. V. Nemtsova M. V. 《Molecular Biology》2003,37(4):591-597
Multiplex methylation-sensitive PCR was employed in studying the methylation of CpG islands in the R1, p16/CDKN2, p15/CDKN2, p14/ARF, DH1, MGMT, HIC1, and N33 promoter regions in breast cancer (105 tumors). Methylation was often observed for the two major suppressor genes involved in controlling the cell cycle through the Cdk–Rb–E2F signaling pathway, R1 (18/105, 17%) and p16 (59/105, 56%); both genes were methylated in 13 tumors. Methylation involved p15 in two (2%) tumors; CDH1, in 83 (79%) tumors; MGMT, in eight (8%) tumors, and N33, in nine (9%) tumors. The p14 promoter was not methylated in the tumors examined. 相似文献
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Loginov V. I. Malyukova A. V. Seryogin Y. A. Hodyrev D. S. Kazubskaya T. P. Ermilova V. D. Garkavtseva R. F. Kisselev L. L. Zabarovsky E. R. Braga E. A. 《Molecular Biology》2004,38(4):549-560
The methylation of the promoter CpG island of the RASSF1A tumor suppressor gene in primary tumors of 172 Muscovites with renal cell carcinoma (RCC), breast cancer (BC), or ovarian epithelial tumors (OET) was assayed by means of methylation-specific PCR (MSP) and PCR-based methylation-sensitive restriction enzyme analysis (MSRA). The MSP, MSRA, and previous bisulfite sequencing data correlated significantly with each other (P 10–6 for Spearman's rank correlation coefficients). By MSP and MSRA, the respective methylation frequencies of the RASSF1A promoter were 86% (25/29) and 94% (50/53) in RCC, 64% (18/28) and 78% (32/41) in BC, and 59% (17/29) and 73% (33/45) in OET. Methylation-sensitive restriction enzymes (HpaII, HhaI, Bsh1236I, AciI) increased the analysis sensitivity and made it possible to establish the methylation status for 18 CpG dinucleotides of the RASSF1A promoter region. With the MSRA data, the density of methylation of the CpG island was estimated at 72% in RCC, 63% in BC, and 58% in OET (the product of the number of CpG dinucleotides and the number of specimens with RASSF1A methylation was taken as 100%). Methylation of the RASSF1A promoter region was observed in 11–35% of the DNA specimens from the histologically normal tissue adjacent to the tumor but not in the peripheral blood DNA of 15 healthy subjects. The RASSF1A methylation frequency showed no significant correlation with the stage, grade, and metastatic potential of the tumor. On the other hand, epigenetic modification of RASSF1A was considerably more frequent than hemizygous or homozygous deletions from the RASSF1A region. These results testify that methylation of the RASSF1A promoter region takes place early in carcinogenesis and is a major mechanism inactivating RASSF1A in epithelial tumors. 相似文献
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Hao Shi Ya Li Xiaozhong Wang Cheng Lu Lilan Yang Changmei Gu Jiaqiang Xiong Yangxin Huang Shixuan Wang Meixia Lu 《PloS one》2013,8(10)
Background
The RAS association domain family protein 1a gene (RASSF1A) is one of the tumor suppressor genes (TSG). Inactivation of RASSF1A is critical to the pathogenesis of cancer. Aberrant TSG methylation was considered an important epigenetic silencing mechanism in the progression of ovarian cancer. A number of studies have discussed association between RASSF1A promoter methylation and ovarian cancer. However, they were mostly based on a small number of samples and showed inconsist results, Therefore, we conducted a meta-analysis to better identify the association.Methods
Eligible studies were identified by searching the PubMed, EMBASE, Web of Science, and CNKI databases using a systematic searching strategy. We pooled the odds ratio (ORs) from individual studies using a fixed-effects model. We performed heterogeneity and publication bias analysis simultaneously.Results
Thirteen studies, with 763 ovarian cancer patients and 438 controls were included in the meta-analysis. The frequencies of RASSF1A promoter methylation ranged from 30% to 58% (median is 48%) in the cancer group and 0 to 21% (median is 0) in the control group. The frequencies of RASSF1A promoter methylation in the cancer group were significantly higher than those in the control group. The pooled odds ratio was 11.17 (95% CI = 7.51–16.61) in the cancer group versus the corresponding control group under the fixed-effects model.Conclusion
The results suggested that RASSF1A promoter methylation had a strong association with ovarian cancer. 相似文献11.
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《Cell cycle (Georgetown, Tex.)》2013,12(5):572-574
The tumor suppressor gene RASSF1A is frequently hypermethylated in various tumors. However, how RASSF1A functions in tumor suppression was unknown. Our study shows that RASSF1A regulates the stability of mitotic cyclins and the timing of mitotic progression by inhibiting APC-Cdc20. RASSF1A appears to work in early pro-metaphase, after Emi1 destruction and before activation of the Mad2-dependent spindle checkpoint. Loss of RASSF1A expression induces premature APC activation, thereby resulting in acceleration of mitotic cyclin degradation and mitotic progression as well as induction of mitotic abnormalities. Thus, RASSF1A plays a critical role in mitotic progression and tumor suppression by controlling APC-Cdc20 activity. 相似文献
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Methylation of the RASSF1A gene in human cancers 总被引:10,自引:0,他引:10
Pfeifer GP Yoon JH Liu L Tommasi S Wilczynski SP Dammann R 《Biological chemistry》2002,383(6):907-914
Loss of genetic material from chromosome 3p21.3 is one of the most common and earliest events in the pathogenesis of lung cancer and many other solid tumors. The chromosomal area 3p21.3 is thought to harbor at least one important tumor suppressor gene, which, despite many years of investigation, has remained elusive. In our previous studies, we have identified and cloned a gene from the common homozygous deletion area at 3p21.3. The gene, named RASSF1A (Ras ASSociation domain Family 1A), has homology to a mammalian Ras effector. The RASSF1A gene is epigenetically inactivated in a large percentage of human lung cancers, in particular small cell carcinomas. A high frequency of methylation of RASSF1A is found also in breast cancers, renal cell carcinomas, ovarian, gastric and bladder cancers, and in neuroblastomas. The RASSF1A gene is a candidate for a tumor suppressor gene in 3p21.3. 相似文献
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RASSF1A基因是新近发现的新型候选抑癌基因,其正常表迭能够抑制肿瘤的发生。启动于区域CpG岛异常甲基化可以导致其失活,并在乳腺癌的发生、发展起着重要作用。RASSF1A的甲基化状态检测具有重要的临床意义,有望为乳腺癌的早期诊断、疗效监测、预后判断提供新的参考指标,而逆转RASSF1A的甲基化则可能为乳腺癌治疗提供新的方向。 相似文献
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Huizi Lei Dongling Zou Zheng Li Min Luo Lei Dong Bin Wang Haixin Yin Yanni Ma Changzheng Liu Fang Wang Junwu Zhang Jia Yu Yu Li 《PloS one》2013,8(4)