Effect of interactions of chromatin regulatory elements with different promoters on the regulation of gene expression / 生物工程学报

The effect of altering the promoter region of ubiquitous chromatin-opening element (UCOE) and matrix attachment region (MAR) on stable and efficient expression of genes was investigated. Four different promoters were tested, namely, oct4 containing an enhancer region, sox2 having a CpG island, nanog having no regulatory elements, and CMV containing a CpG island and an enhancer region. Eight reporter plasmids were constructed: pOCT4-UCOE, pOCT4-MAR, pSOX2-UCOE, pSOX2-MAR, pNANOG-UCOE, pNANOG-MAR, pCMV-UCOE, and pCMV-MAR. Stable and efficient expression was observed when UCOE combined with the oct4 promoter, whereas the sox2 was the best promoter suited for MAR. Comparison of the stable clones of oct4-UCOE and sox2-MAR showed that UCOE-regulated expression is more stable and efficient than MAR-regulated expression. When CpG island-containing promoter is linked with UCOE, stable and efficient expression could be observed. These data suggest that an enhancer region in the promoter leads to high, yet unstable expression when combined with UCOE, whereas CpG islands stabilize expression. In conclusion, UCOE and MAR interact with regulatory elements on the promoter by altering the chromatin open state and chromatin loop to regulate gene expression.

Detection of free DNA septin 9 gene methylation in plasma / 中南大学学报(医学版)

OBJECTIVES@#To explore the correlation between cytosine-phosphoric-guanylic (CpG) site of Septin 9 gene and colorectal cancer, and to develop a real-time PCR detection system in plasma in patients with colorectal cancer.@*METHODS@#The methylation of training samples was detected by high-throughput sequencing technology, and the sites highly consistent with the clinical information of colorectal cancer were identified. Then the detection system of real-time PCR was designed to analyze the consistency of plasma and tissue based on methylationa sensitive enzyme digestion. Finally, 100 clinical trials were conducted to evaluate the performance of the detection system with the methylation sensitive enzyme digestion-real-time PCR.@*RESULTS@#The highly consistent sites, which were selected by high-throughput sequencing from 71 training set samples, was the 38th CpG. Based on the detection region, the screened methylation sensitive enzymes were @*CONCLUSIONS@#The 38th CpG site of Septin 9 detected by the detection system of methylation sensitive enzyme digestion-real-time PCR can highly predict the occurrence of colorectal cancer with great clinical application value.

Quantitative analysis of DNA methylation by pyrosequencing and MassARRAY technique for age estimation: a comparative study / 南方医科大学学报

OBJECTIVE@#To study the difference in age estimation based on quantitative analysis of DNA methylation by MassARRAY and pyrosequencing techniques.@*METHODS@#The methylation levels of 9 CpG sites from two independent whole blood sample sets (containing 65 and 62 samples) were detected using MassARRAY and pyrosequencing techniques. Z-score transformation was used to remove the batch effects of different techniques, and a linear regression model was used for age prediction.@*RESULTS@#For age prediction using the MassARRAY system, the 65 samples showed a mean absolute difference (MAD) of 2.49 years before Z-score transformation of the data and 2.44 years after the transformation, similar to the results in the 62 samples (MAD of 3.36 years before and 3.42 years after Z-score transformation). For data typed from pyrosequencing, the 65 samples showed a MAD of 4.20 years before and 2.76 years after data Z-score transformation, also similar to the results in the 62 samples (MAD of 3.92 years before and 3.63 years after data transformation).@*CONCLUSIONS@#Z-score transformation can effectively reduce the system batch effect between MassARRAY and pyrosequencing. Data from the MassARRAY system allows direct age estimation without further data processing, while the pyrosequencing data may increase the error in age estimation, which can be corrected by Z-score transformation of the data.

Assessment of changes in the brca2 and p53 genes in breast invasive ductal carcinoma in northeast Brazil

BACKGROUND: BRCA protein interacts with at least 13 different proteins that have been implicated with cancer susceptibility and loss of BRCA function is correlated to sensitivity to DNA crosslinking agents in preclinical models. RESULTS: BRCA2 methylation frequency was 44%, p53 Pro22 allele frequency was 32% and heterozygous frequency of Arg/Pro72 genotype was 60% which could be associated as risk factor for metastasis (p = 0.046 OR = 4.190). Regarding to polymorphism of codon 249 the frequency of Arg249 allele presented 82% which was considered not statistically significant. CONCLUSIONS: There was not statistical significance to BRCA2 promoter methylation with any parameters chosen. However, our findings suggest that patients who present heterozygous genotype at codon 72 of p53 gene may have a major susceptibility to any type of metastasis and this could serve as potential auxiliary biomarker for poor prognosis.

The clinical importance of serrated lesions of the colorectum / La importancia clínica de las lesiones serradas del colon y recto

Colorectal cancer (CRC) is the third most common cancer in the world. Fortunately, it is also proven to be one of the most preventable cancers, in large part due to the utilization of CRC screening. Historically, it was believed that the adenomatous polyp was the only precursor to carcinoma of the colorectum. Within the last decade, it has been shown that approximately 20-30% of sporadic colon cancers arise through a distinct molecular pathway called CpG Island Methylation (CIMP) which is due to widespread DNA methylation. There is strong evidence that serrated polyps are the precursor lesions for colon cancers arising through the CIMP pathway.

Cáncer Colorectal (CRC) es el tercer cáncer más común en el mundo (1). Afortunadamente también se ha probado que es el cáncer que más se puede prevenir, en gran parte debido al "screening" del CRC. Históricamente, se creía que el pólipo adenomatoso era el único precursor del carcinoma de colon y recto. En la última década se ha demostrado que aproximadamente el 20 al 30% de los cánceres colónicos esporádicos se derivan de una vía molecular diferente llamada Metilación de las Islas CpG (CIMP) que es debida a una extensión de la metilación del DNA.Actualmente hay una fuerte evidencia que los pólipos serrados son las lesiones precursoras de cáncer de colon surgiendo desde la vía CIMP.

Genes con islas CpG amplificados con la mezcla formamida, albúmina sérica bovina y dimetilsulfóxido / CG-rich genes amplified with the formamide, bovine seric albumin y dimethylsulfoxide mix / Genes com Ilhas CpG amplificados com a mistura formamida, albumina sérica bovina, e dimetilsulfóxido

Diversos aditivos químicos han sido utilizados para garantizar la polimerización de genes con islas CpG. El objetivo de este trabajo fue diseñar una mezcla potenciadora de PCR para amplificar genes con islas CpG. Con ese fin se analizaron fragmentos de los genes IRS2 y HNF1a con el programa EMBOSS CpG Report. Los iniciadores se diseñaron con el programa Primer 3 y se analizaron con el programa e-PCR. Se usaron tres aditivos químicos: Albúmina sérica bovina (0,1µg/µL), dimetilsulfóxido (5%) y formamida (5%) para 5 ensayos de PCR: dos usando un solo aditivo, dos combinando dos aditivos y uno combinando tres aditivos. Las amplificaciones con las mezclas se realizaron con las enzimas Taq Nativa, taq Recombinante y Taq Platinum. La calidad de los amplicones se probó por secuenciación. Fragmentos sin islas CpG (HNF-1a) amplificaron con las tres enzimas, sin el uso de los aditivos pero presentaron problemas de pureza en la secuenciación. Los fragmentos del gen IRS2 con islas CpG amplificaron sólo con la combinación de tres aditivos dimetilsulfóxido, albúmina sérica bovina y formamida, independientemente de la enzima usada, las secuencias fueron limpias. Se concluye que la mezcla de tres aditivos es una solución que permite obtener amplicones de alta calidad en genes con islas CpG, con cromatogramas limpios en la secuenciación.

Several chemical additives have been used to assure polymerization in CpG islands.The aim of the present work was to design a PCR enhancer mixture in order to amplify GC-rich genes. Fragments of IRS2 and HNF1a genes were analyzed using EMBOSS CpG Report Software. Primers were designed with the Primer3 Software and were tested with ePCR Software. Three additives were used: BSA (0.1µg/µL), DMSO (5%) and formamide (5%), in five PCR assays, two using one additive, two combining two additives and one with all additives. DNA sequences were amplified with the following enzymes: Native Taq, recombinant Taq and platinum Taq DNA polymerase. Amplicon quality was examined by sequencing. HNF1a gene was amplified without additives; however, the sequences were not amplified and showed purity problems in sequencing. The gene fragments IRS2 with CpG islands were amplified with additives DMSO, BSA and Formamida mixture, notwithstanding the enzyme used. These sequences were clean. DMSO-BSA-Formamide mixture can be a solution to obtain GC-rich DNA amplicons with such a high quality that it generates neat chromatograms during sequencing.

Diversos aditivos químicos têm sido utilizados para garantir a polimerização de genes com ilhas CpG. O objetivo do trabalho foi desenhar uma mistura que potencie PCR para amplificar genes com ilhas CpG. Para esta finalidade foram analisados fragmentos dos genes IRS2 e HNF1a com o programa EMBOSS CpG Report. Os iniciadores foram desenhados com o programa Primer 3 e se analisaram com o programa e-PCR. Foram utilizados três aditivos químicos: Albumina sérica bovina (0,1µg/µlL, Dimetilsulfóxido (5%) e formamida (5%) para 5 ensaios de PCR: dois usando um único aditivo, dois combinando dois aditivos e um combinando três aditivos. As amplificações com as misturas se realizaram com as enzimas, Taq Nativa, taq Recombinante e Taq Platinum. A qualidade das ampliações foi provada por sequenciação. Fragmentos sem ilhas CpG (HNF-1a) amplificaram com as três enzimas, sem o uso dos aditivos porém apresentaram problemas de pureza na sequenciação. Os fragmentos do gene IRS2 com ilhas CpG ampli­ficaram apenas com a combinação de três aditivos dimetilsulfóxido, albumina sérica bovina e formamida, independentemente da enzima usada, as sequências foram limpas. A conclusão que a mistura de três aditivos é uma solução que permite obter ampliações de alta qualidade em genes com ilhas CpG, com cromatogramas limpos na secuenciação.

Hypomethylation of tumor suppressor genes in odontogenic myxoma

Odontogenic myxoma (OM) is an ectomesenchymal benign odontogenic tumor characterized by spindle or stellate-shaped cells embedded in an abundant myxoid or mucoid extracellular matrix. DNA methylation is characterized by the addition of methyl groups in cytosines within CpG islands in the promoter gene. DNA methylation can decrease the expression of tumor suppressor genes and contribute to the development of neoplastic lesions. The aim of study was to evaluate the methylation pattern of the tumor suppressor genes P16 (CDKN2A), P21 (CDKN1A), P27 (CDKN1B), P53 (TP53) and RB1 in OM and dental pulp. Methylation was evaluated using methylation-specific polymerase chain reaction (PCR). The transcription was studied in some cases by using reverse transcription quantitative PCR. A higher frequency of unmethylated P27, P53, and RB1 samples was observed in the OM when compared with the dental pulp. OM expressed mRNA of all the genes evaluated. Considering all the samples together, the expression of Rb was higher in the unmethylated samples compared with the partially methylated samples. This investigation revealed hypomethylation of the genes P27, P53, and RB1 in OM. In addition, methylation of tumor suppressor genes was found to be an usual event in normal dental pulp.

O mixoma odontogênico (MO) é um tumor odontogênico benigno de origem mesenquimal caracterizado pela presença de células fusiformes ou estreladas dispostas em abundante matriz extracelular mucóide. A metilação do DNA é caracterizada pela adição de grupos metil em citosinas constituintes de ilhas CpG na região promotora do gene. A metilação pode diminuir a expressão de genes supressores de tumor e contribuir para o desenvolvimento de lesões neoplásicas. O objetivo deste trabalho foi avaliar o padrão de metilação nos genes P16 (CDKN2A), P21 (CDKN1A), P27 (CDKN1B), P53 (TP53), RB1 nos MO e na polpa dental. A metilação foi avaliada pela reação em cadeia da polimerase específica para a metilação. A transcrição dos genes foi estudada em alguns casos pela reação da transcriptase reversa (PCR quantitativa). Uma maior frequência de amostras não metiladas para os genes P27, P53 e RB1 foi observada nos MO quando comparados à polpa dental. Os MO expressaram RNAm de todos os genes avaliados. Considerando todas as amostras juntas, a expressão de Rb foi maior em amostras não metiladas comparadas as amostras parcialmente metiladas. Esta investigação mostrou a hipometilação dos genes P27, P53 e RB1 nos MO. Adicionalmente, a metilação nos genes supressores de tumor é um evento frequente em polpa dental normal.

Characterization & evolutionary analysis of human CD36 gene.

Background and objectives: Understanding evolutionary genetic details of immune system genes responsible for infectious diseases is of prime importance concerning disease pathogenecity. Considering malaria as a devastating disease in the world including India, detail evolutionary understanding on human immune system gene is essential. The primary aim of this study was to initiate work on one such gene, the human CD36 gene responsible in malaria pathogenesis. Methods: DNA sequences of the human CD36 gene was retrieved from public domain and fifi ne-scale details were characterized. Both comparative and evolutionary analyses were performed with sequences from six other taxa (5 mammalian one avian) where CD36 homologs are present. Different statistical analyses were also performed. Results: Differential distribution in number and length of exons and introns was detected in CD36 gene across seven taxa. The CpG islands were also found to be distributed unevenly across the gene and taxa. Neighbour-joining tree was constructed and it was observed that the chimpanzee and human are diverged at the CD36 gene relatively recently. The chicken, Gallus gallus was found to be diverged from rest of the taxa signifi cantly. Also copy number variation was observed across different taxa. Interpretation & conclusions: Comparative genomic study of a human immune system gene CD36 show relationships among different taxa at the evolutionary level. The information can be of help to study genetic diversity in malaria endemic zones and to correlate it with malaria pathogenecity.

Perspective of DNA methylation in forensic genetics and new progress of its detection methods / 法医学杂志

As an important epigenetic marker, DNA methylation has exhibited a valuable perspective in the fields of forensic genetics, especially in cases of paternity identification in duos and discrimination of monozygotic twins, which may be a useful complement to the classic genetics markers, such as short tandem repeats, single nucleotide polymorphism. Various methods for DNA methylation detection have been developed and validated based on methylation sensitive restriction endonuclease, bisulfite modification or methylation-CpG binding domain protein. Methylation-sensitive single nucleotide primer extension, real-time PCR, methylation-specific PCR, methylation-specific multiplex ligation-dependent probe amplification and the Illumina's Human Methylation 27 have been all applicable for analyzing identified CpG loci or short sequences, and can be effectively used in forensic laboratory. However, Amplification of Inter-Methylated Sites (AIMS), Hpa II tiny fragment Enrichment by Ligation-mediated PCR (HELP) or Combination of Methylated-DNA Precipitation and Methylation-Sensitive Restriction Enzymes (COMPARE-MS) are useful in genome wide methylation scanning to find new CpG loci which may be valuable in forensic fields.

DNA Methylation and Expression Patterns of Key Tissue-specific Genes in Adult Stem Cells and Stomach Tissues

CpG-island margins and non-island-CpG sites round the transcription start sites of CpG-island-positive and -negative genes are methylated to various degrees in a tissue-specific manner. These methylation-variable CpG sites were analyzed to delineate a relationship between the methylation and transcription of the tissue-specific genes. The level of tissue-specific transcription was estimated by counting the number of the total transcripts in the SAGE (serial analysis of gene expression) database. The methylation status of 12 CpG-island margins and 21 non-island CpG sites near the key tissue-specific genes was examined in pluripotent stromal cells obtained from fat and bone marrow samples as well as in lineage-committed cells from marrow bulk, stomach, colon, breast, and thyroid samples. Of the 33 CpG sites examined, 10 non-island-CpG sites, but none of the CpG-island margins were undermethylated concurrent with tissue-specific expression of their nearby genes. The net methylation of the 33 CpG sites and the net amount of non-island-CpG gene transcripts were high in stomach tissues and low in stromal cells. The present findings suggest that the methylation of the non-island-CpG sites is inversely associated with the expression of the nearby genes, and the concert effect of transitional-CpG methylation is linearly associated with the stomach-specific genes lacking CpG-islands.

Biomarkers for Colorectal Cancer Treatment / 대한소화기학회지

Individualized tailored therapy is a currently pursuing direction for improving the outcome of patients with colorectal cancer. Targeted therapy is the potential strategy to reach this goal by evaluating status of the presumed targets and their related effector molecules and by maximizing the efficacy of chemotherapeutic agents with less toxicity in individual patient. Numerous hurdles should be overcome, however, because therapeutic outcome can be affected by multiple components; tumor characteristics such as somatic mutations at the DNA, RNA, and protein levels; patient characteristics like germline genetic polymorphisms in enzymes linked to drug metabolism; and environmental factors that include diet and physical activity. Currently, large numbers of potential biomarkers have been proposed but have not yet accomplished supporting evidences for their routine usage in clinics. Therefore, clinical trials driven by molecular targets and relevant biomarkers for the understanding of the conflicting data are needed to make markers available in clinical practice.

DNA methylation profile in diffuse type gastric cancer: evidence for hypermethylation of the BRCA1 promoter region in early-onset gastric carcinogenesis

Diffuse type gastric carcinoma is the most aggressive type of gastric cancer. This type of tumor is not preceded by precancerous changes and is associated with early-onset and hereditary syndromes. To test the hypothesis that DNA methylation profile would be useful for molecular classification of the diffuse type gastric carcinoma, DNA methylation patterns of the CpG Island of 17 genes were studied in 104 cases and 47 normal adjacent gastric mucosa by Methylation-specific PCR, Immunohistochemistry and Hierarchicalclustering analysis. The most frequent methylated genes were FHIT, E-cadherin, BRCA1 and APC (>50%),followed by p14, p16, p15, p73, MGMT and SEMA3B (20-49%). Hierarchical clustering analysis reveals four groups with different clinical features. The first was characterized by hypermethylation of BRCA1 and younger age (<45 years old), and the second by hypermethylation of p14 and p16 genes, male predominance and Epstein-Barr virus infection. The third group was characterized by hypermethylation of FHIT and antrum located tumors and the fourth was not associated with any clinical variables. In normal adjacent mucosa only the p73 gene was significantly less methylated in comparison to tumor mucosa. DNA methylation identified subgroups of diffuse type gastric cancer. Hypermethylation of BRCA1 associated with young age suggests a role in early-onset gastric carcinoma.

Chromosomal Losses are Associated with Hypomethylation of the Gene-Control Regions in the Stomach with a Low Number of Active Genes

Transitional-CpG methylation between unmethylated promoters and nearby methylated retroelements plays a role in the establishment of tissue-specific transcription. This study examined whether chromosomal losses reducing the active genes in cancers can change transitional-CpG methylation and the transcription activity in a cancer-type-dependent manner. The transitional-CpG sites at the CpG-island margins of nine genes and the non-island-CpG sites round the transcription start sites of six genes lacking CpG islands were examined by methylation-specific polymerase chain reaction (PCR) analysis. The number of active genes in normal and cancerous tissues of the stomach, colon, breast, and nasopharynx were analyzed using the public data in silico. The CpG-island margins and non-island CpG sites tended to be hypermethylated and hypomethylated in all cancer types, respectively. The CpG-island margins were hypermethylated and a low number of genes were active in the normal stomach compared with other normal tissues. In gastric cancers, the CpG-island margins and non-island-CpG sites were hypomethylated in association with high-level chromosomal losses, and the number of active genes increased. Colon, breast, and nasopharyngeal cancers showed no significant association between the chromosomal losses and methylation changes. These findings suggest that chromosomal losses in gastric cancers are associated with the hypomethylation of the gene-control regions and the increased number of active genes.

Methylation Profiles of CpG Island Loci in Major Types of Human Cancers

Several reports have described aberrant methylation in various types of human cancers. However, the interpretation of methylation frequency in various human cancers has some limitations because of the different materials and methods used for methylation analysis. To gain an insight into the role of DNA hypermethylation in human cancers and allow direct comparison of tissue specific methylation, we generated methylation profiles in 328 human cancers, including 24 breast, 48 colon, 61 stomach, 48 liver, 37 larynx, 24 lung, 40 prostate, and 46 uterine cervical cancer samples by analyzing CpG island hypermethylation of 13 genes using methylation-specific PCR. The mean numbers of methylated genes were 6.5, 4.4, 3.6, 3.4, 3.1, 3.1, 3.1, and 2.1 in gastric, liver, prostate, larynx, colon, lung, uterine cervix, and in breast cancer samples, respectively. The number of genes that were methylated at a frequency of more than 40% in each tumor type ranged from nine (stomach) to one (breast). Generally genes frequently methylated in a specific cancer type differed from those methylated in other cancer types. The findings indicate that aberrant CpG island hypermethylation is a frequent finding in human cancers of various tissue types, and each tissue type has its own distinct methylation pattern.

Promoter hypermethylation of DNA repair gene MGMT in laryngeal squamous cell carcinoma / 华中科技大学学报（医学）（英德文版）

The relationship between hypermethylation of CpG islands in the promoter regions of O6-methylguanine DNA methyltransferase (MGMT) genes and laryngeal squamous cell carcinoma was explored. Methylation-specific PCR and semi-quantitative RT-PCR were used to study the promoter methylation and mRNA expression of the MGMT gene in laryngeal carcinoma tissues, tissues adjacent to the tumor and normal laryngeal tissues. Hypermethylation of MGMT gene was detected in 16 samples of 46 (34.8%) laryngeal squamous cell carcinoma samples. However, the MGMT hypermethylation was not detected in all tissues adjacent to the tumors and normal tissues. No significant difference in MGMT gene hypermethylation was found in samples with different histological grades (chi2 = 3.130, P = 0.077) or in samples from patients with different TNM status (chi2 = 3.957, P = 0.138). No expression of MGMT mRNA was detected in all hypermethylated laryngeal carcinoma tissues. The expression of MGMT mRNA was detected in all unmethylated laryngeal carcinoma tissues, tissues adjacent to the tumors and normal tissues. It suggests that MGMT gene promoter hypermethylation is associated with MGMT gene transcription loss in laryngeal carcinoma tissues and possibly plays an important role in carcinogenesis of laryngeal tissues.

The prima donna of epigenetics: the regulation of gene expression by DNA methylation

This review focuses on the mechanisms of DNA methylation, DNA methylation pattern formation and their involvement in gene regulation. Association of DNA methylation with imprinting, embryonic development and human diseases is discussed. Furthermore, besides considering changes in DNA methylation as mechanisms of disease, the role of epigenetics in general and DNA methylation in particular in transgenerational carcinogenesis, in memory formation and behavior establishment are brought about as mechanisms based on the cellular memory of gene expression patterns.

Applications of DNA methylation markers in forensic medicine / 法医学杂志

DNA methylation is a post-replication modification that is predominantly found in cytosines of the dinucleotide sequence CpG. Epigenetic information is stored in the distribution of the modified base 5-methylcytosine. DNA methylation profiles represent a more chemically and biologically stable source of molecular diagnostic information than RNA or most proteins. Recent advances attest to the great promise of DNA methylation markers as powerful future tools in the clinic. In the past decade, DNA methylation analysis has been revolutionized by two technological advances--bisulphite modification of DNA and methylation-specific polymerase chain reaction (MSP). The methylation pattern of human genome is space-time specific, sex-specific, parent-of-origin specific and disease specific, providing us an alternative way to solve forensic problems.

Relationship Between the Extent of Chromosomal Losses and the Pattern of CpG Methylation in Gastric Carcinomas

The extent of unilateral chromosomal losses and the presence of microsatellite instability (MSI) have been classified into high-risk (high- and baseline-level loss) and low-risk (low-level loss and MSI) stem-line genotypes in gastric carcinomas. A unilateral genome-dosage reduction might stimulate compensation mechanism, which maintains the genomic dosage via CpG hypomethylation. A total of 120 tumor sites from 40 gastric carcinomas were examined by chromosomal loss analysis using 40 microsatellite markers on 8 chromosomes and methylation analysis in the 13 CpG (island/non-island) regions near the 10 genes using the bisulfite-modified DNAs. The high-level-loss tumor (four or more losses) showed a tendency toward unmethylation in the Maspin, CAGE, MAGE-A2 and RABGEF1 genes, and the other microsatellite-genotype (three or fewer losses and MSI) toward methylation in the p16, hMLH1, RASSF1A, and Cyclin D2 genes (p<0.05). The non-island CpGs of the p16 and hMLH1 genes were hypomethylated in the high-level-loss and hypermethylated in the non-high-level-loss sites (p<0.05). Consequently, hypomethylation changes were related to a high-level loss, whereas the hypermethylation changes were accompanied by a baseline-level loss, a low-level loss, or a MSI. This indicates that hypomethylation compensates the chromosomal losses in the process of tumor progression.

Cancer Epigenetics / 대한소화기학회지

Knowledge regarding molecular events of cancer development has been rapidly accumulated during the last decade. The discovery of tumor suppressor gene-silencing by aberrant promoter CpG island hypermethylation and histone-directed chromatin remodeling has led epigenetics to its recognition as an important alternative mechanism for carcinogenesis. Epigenetics does not involve changes in nucleotide sequences, but it affects on genetic composition in many ways. Cancer cells integratively co-opt genetic and epigenetic mechanisms to acquire different aspects of carcinogenetic phenotypes. Since epigenetic changes can be reversed with relative ease, the research of cancer epigenetics provides great potential for new therapeutic regimens.