DNA Methylation and Inactivation of Tumor Suppressor Genes

2015 ◽  
pp. 152-160
Author(s):  
Adrian Merlo ◽  
James G. Herman
Keyword(s):  
Dna Methylation ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Suppressor Genes

scholarly journals Targeting DNA methylation for treating triple-negative breast cancer

2019 ◽  
Vol 20 (16) ◽  
pp. 1151-1157 ◽  
Author(s):  
Jia Yu ◽  
Jacqueline Zayas ◽  
Bo Qin ◽  
Liewei Wang
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Tumor Suppressor ◽  
Triple Negative Breast Cancer ◽  
Targeted Therapies ◽  
Tumor Suppressor Genes ◽  
Dna Methyltransferase ◽  
Triple Negative ◽  
Suppressor Genes ◽  
Dna Methyltransferase Inhibitors

Triple-negative breast cancer (TNBC) accounts for 15–20% of all invasive breast cancers and tends to have aggressive histological features and poor clinical outcomes. Unlike, estrogen receptor- or HER2-positive diseases, TNBC patients currently lack the US FDA-approved targeted therapies. DNA methylation is a critical mechanism of epigenetic modification. It is well known that aberrant DNA methylation contributes to the malignant transformation of cells by silencing critical tumor suppressor genes. DNA methyltransferase inhibitors reactivate silenced tumor suppressor genes and result in tumor growth arrest, with therapeutic effects observed in patients with hematologic malignancies. The antitumor effect of these DNA methyltransferase inhibitors has also been explored in solid tumors, especially in TNBC that currently lacks targeted therapies.

Aberrant DNA methylation of some tumor suppressor genes in lung cancers from workers with chromate exposure

2010 ◽  
Vol 50 (2) ◽  
pp. 89-99 ◽  
Author(s):  
Abdellah H. K. Ali ◽  
Kazuya Kondo ◽  
Toshiaki Namura ◽  
Yoshitaka Senba ◽  
Hiromitsu Takizawa ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Suppressor Genes ◽  
Lung Cancers ◽  
Aberrant Dna Methylation ◽  
Chromate Exposure

DNA Methylation Changes Following 5-Azacitidine Treatment in Patients with Myelodysplastic Syndrome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2791-2791
Author(s):  
Huong Thi Thanh Tran ◽  
Hee Nam Kim ◽  
Yeo-Kyeoung Kim ◽  
Jae-Sook Ahn ◽  
Il-Kwon Lee ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Dna Methyltransferase ◽  
Conflicts Of Interest ◽  
Control Group ◽  
Disease Pathogenesis ◽  
Suppressor Genes ◽  
Clinical Responses ◽  
Dependent Probe

Abstract Abstract 2791 Poster Board II-767 Gene silencing by promoter methylation is as potent as functional inactivating of tumor suppressor genes by mutations. DNA methyltransferase inhibitor, 5-azacytidine (AC) and 5-aza-2 -deoxycitidine (DAC), which is proved to be effective in myelodysplastic syndromes (MDS) can induce re-expression in cancer; however their mechanism remains controversial. 25 tumor suppressor genes by MS-MLPA (methylation-specific multiplex ligation-dependent probe amplification) were analyzed in 44 MDS patients treated Vidaza® (5-azacitidine, AC). Hypermethylation of at least one gene was detected in 9/44 patients (20.5%), including four genes CDKN2B, FHIT, ESR1 and IGSF4. Interestingly, of 9 hypermethylated patients, 8 patients showed demethylation in concordance with their clinical responses after three to five cycles AC treatment. Lack or decrease methylation was observed in four patients with hematological improvements. Persistence methylation was observed in four others who became AML transformation or no response after treatment, especially reinforcing methylated gene in a case progressed to leukemia later. Our study also founds out IGSF4 gene hypermethylation in MDS as a first report. Additionally, mRNA expression of CDKN2B, IGSF4, and ESR1 in MDS were significantly lower than those in the control group (p < 0.05). Our results suggest that the methylation changes of specific genes contributes to disease pathogenesis and might present a molecular marker that can be used to monitor the efficacy of AC treatment in MDS. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Ambient PM exposure and DNA methylation in tumor suppressor genes: a cross-sectional study

2011 ◽  
Vol 8 (1) ◽  
pp. 25 ◽  
Author(s):  
Lifang Hou ◽  
Xiao Zhang ◽  
Letizia Tarantini ◽  
Francesco Nordio ◽  
Matteo Bonzini ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Suppressor Genes

scholarly journals Chrysin Modulates Aberrant Epigenetic Variations and Hampers Migratory Behavior of Human Cervical (HeLa) Cells

2022 ◽  
Vol 12 ◽  
Author(s):  
Ritu Raina ◽  
Abdulmajeed G. Almutary ◽  
Sali Abubaker Bagabir ◽  
Nazia Afroze ◽  
Sharmila Fagoonee ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Suppressor ◽  
Histone Modification ◽  
Hela Cells ◽  
Tumor Suppressor Genes ◽  
Methylation Status ◽  
Global Dna Methylation ◽  
Dependent Manner ◽  
Suppressor Genes ◽  
Protein Levels

Purpose: Plant-derived phytochemicals have shown epigenetic modulatory effect in different types of cancer by reversing the pattern of DNA methylation and chromatin modulation, thereby restoring the function of silenced tumor-suppressor genes. In the present study, attempts have been made to explore chrysin-mediated epigenetic alterations in HeLa cells.Methods: Colony formation and migration assays followed by methylation-specific PCR for examining the methylation status of CpG promoters of various tumor-suppressor genes (TSGs) and the expression of these TSGs at the transcript and protein levels were performed. Furthermore, global DNA methylation; biochemical activities of DNA methyltransferases (DNMTs), histone methyl transferases (HMTs), histone deacetylases (HDACs), and histone acetyl transferases (HATs) along with the expression analysis of chromatin-modifying enzymes; and H3 and H4 histone modification marks analyses were performed after chrysin treatment.Results: The experimental analyses revealed that chrysin treatment encourages cytostatic behavior as well as inhibits the migration capacity of HeLa cells in a time- and dose-dependent manner. Chrysin reduces the methylation of various tumor-suppressor genes, leading to their reactivation at mRNA and protein levels. The expression levels of various chromatin-modifying enzymes viz DNMTs, HMTs, HDACs, and HATS were found to be decreased, and H3 and H4 histone modification marks were modulated too. Also, reduced global DNA methylation was observed following the treatment of chrysin.Conclusion: This study concludes that chrysin can be used as a potential epigenetic modifier for cancer treatment and warrants for further experimental validation.

scholarly journals Hypermethylated promoters of tumor suppressor genes were identified in Crohn’s disease patients

2020 ◽  
Vol 18 (3) ◽  
pp. 297-305
Author(s):  
Tae-Oh Kim ◽  
Yu Kyeong Han ◽  
Joo Mi Yi
Keyword(s):  
Dna Methylation ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Tumor Suppressor ◽  
Environmental Factors ◽  
Tumor Suppressor Genes ◽  
Bisulfite Sequencing ◽  
Sequencing Analysis ◽  
Gene Promoters ◽  
Suppressor Genes

Background/Aims: Overwhelming evidence suggests that inflammatory bowel disease (IBD) is caused by a complicated interplay between the multiple genes and abnormal epigenetic regulation in response to environmental factors. It is becoming apparent that epigenetic factors are significantly associated with the development of the disease. DNA methylation remains the most studied epigenetic modification, and hypermethylation of gene promoters is associated with gene silencing.Methods: DNA methylation alterations may contribute to the many complex diseases development by regulating the interplay between external and internal environmental factors and gene transcriptional expression. In this study, we used 15 tumor suppressor genes (TSGs), originally identified in colon cancer, to detect promoter methylation in patients with Crohn’s disease (CD). Methylation specific polymerase chain reaction and bisulfite sequencing analyses were performed to assess methylation level of TSGs in CD patients.Results: We found 6 TSGs (<i>sFRP1, sFRP2, sFRP5, TFPI2, Sox17</i>, and <i>GATA4</i>) are robustly hypermethylated in CD patient samples. Bisulfite sequencing analysis confirmed the methylation levels of the <i>sFRP1, sFRP2, sFRP5, TFPI2, Sox17</i>, and <i>GATA4</i> promoters in the representative CD patient samples.Conclusions: In this study, the promoter hypermethylation of the TSGs observed indicates that CD exhibits specific DNA methylation signatures with potential clinical applications for the noninvasive diagnosis of IBD and the prognosis for patients with IBD.

scholarly journals DNA Methylation of Tumor Suppressor Genes in Pituitary Neuroendocrine Tumors

2018 ◽  
Vol 104 (4) ◽  
pp. 1272-1282 ◽  
Author(s):  
Araceli García-Martínez ◽  
Johana Sottile ◽  
Laura Sánchez-Tejada ◽  
Carmen Fajardo ◽  
Rosa Cámara ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Suppressor ◽  
Neuroendocrine Tumors ◽  
Tumor Suppressor Genes ◽  
Suppressor Genes

Detection and Analysis of RNAs Expression Profile for Methylated Candidate Tumor Suppressor Genes in Nasopharyngeal Carcinoma

2019 ◽  
Vol 19 (6) ◽  
pp. 772-782
Author(s):  
Shuang Zhao ◽  
Ye Zhang ◽  
Xujun Liang ◽  
Maoyu Li ◽  
Fang Peng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Nasopharyngeal Carcinoma ◽  
Tumor Suppressor ◽  
Promoter Methylation ◽  
Tumor Suppressor Genes ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Suppressor Genes ◽  
Multiple Tumor

Background:DNA methylation, which acts as an expression regulator for multiple Tumor Suppressor Genes (TSGs), is believed to play an important role in Nasopharyngeal Carcinoma (NPC) development.Methods:We compared the effects of 5-aza-2-deoxycytidine (decitabine, DAC) on gene expression using RNA sequencing in NPC cells.Results:We analyzed Differentially Expressed Genes (DEGs) in NPC cells using DAC demethylation treatment and found that 2182 genes were significantly upregulated (≥ 2-fold change), suggesting that they may play a key role in cell growth, proliferation, development, and death. For data analysis, we used the Gene Ontology database and pathway enrichment analysis of the DEGs to discover differential patterns of DNA methylation associated with changes in gene expression. Furthermore, we evaluated 74 methylated candidate TSGs from the DEGs in NPC cells and summarized these genes in several important signaling pathways frequently disrupted by promoter methylation in NPC tumorigenesis.Conclusion:Our study analyzes the DEGs and identifies a set of genes whose promoter methylation in NPC cells is reversed by DAC. These genes are potential substrates of DNMT inhibitors and may serve as tumor suppressors in NPC cells.

DNA methylation analysis of tumor suppressor genes in monoclonal gammopathy of undetermined significance

2009 ◽  
Vol 89 (2) ◽  
pp. 191-199 ◽  
Author(s):  
Carmen Stanganelli ◽  
Jorge Arbelbide ◽  
Dorotea Beatriz Fantl ◽  
Claudia Corrado ◽  
Irma Slavutsky
Keyword(s):  
Dna Methylation ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Monoclonal Gammopathy ◽  
Methylation Analysis ◽  
Suppressor Genes ◽  
Dna Methylation Analysis ◽  
Undetermined Significance
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