PurposeTo measure the hypermethylation of four genes in primary tumors and paired plasma samples to determine the feasibility of gene promoter hypermethylation markers for detecting breast cancer in the plasma.Materials and MethodsDNA was extracted from the tumor tissues and peripheral blood plasma of 34 patients with invasive breast ...

Recent studies have shown that promoter hypermethylation of tumor suppressor genes is an important factor in carcinogenesis of several human organs. The purpose of this study was to examine the methylation status of CHFR, a novel cell cycle regulatory gene, in both primary oral cancer tumors and the adjacent normal mucosa, and to clarify the relation ...

Promoter hypermethylation-mediated silencing of tumor suppressor genes (TSGs) is a hallmark of oncogenesis. Oxidored-nitro domain-containing protein 1 (NOR1) is a candidate TSG that is downregulated in nasopharyngeal carcinoma (NPC). In the present study, we identified a functional NOR1 promoter that is regulated by heat shock factor 1 ...

INTRODUCTION: This study examined the contribution of promoter hypermethylation to the pathogenesis of respiratory papillomatosis (RP), including recurrences (RRP) and progression to squamous cell carcinoma (SSC). MATERIALS AND METHODS: A retrospective cohort of 25 laryngeal papilloma cases included 21 RRP, two of which progressed to SCC. ...

Aberrant methylation of CpG islands in promoter regions of tumor suppressor genes (TSG) has been demonstrated in epithelial origin tumors. However, the methylation profiling of tumor-related gene promoter regions in cutaneous melanoma tumors has not been reported. Seven known or candidate TSGs that are frequently ...

Aberrant methylation of CpG islands in promoter regions of tumor suppressor genes (TSG) has been demonstrated in epithelial origin tumors. However, the methylation profiling of tumor-related gene promoter regions in cutaneous melanoma tumors has not been reported. Seven known or candidate TSGs that are frequently ...

IntroductionFemale germline BRCA gene mutation carriers are at increased risk for developing breast cancer. The purpose of our study was to establish whether healthy BRCA mutation carriers demonstrate an increased frequency of aberrant gene promoter hypermethylation in ductal lavage (DL) fluid, compared with predictive genetic test ...

Zygote arrest 1 (ZAR1) is a novel maternal-effect gene of crucial importance during the oocyte-to-embryo transition. Comprehensive methylation analysis of tumor-specific differently methylated regions in human malignant melanomas has recently led to the identification of non-promoter hypermethylation of the ZAR1 gene that had never been identified as an ...

Aberrant methylation of CpG islands in the promoter regions of tumour cells results in loss of gene function. In addition to genetic lesions, changes in the methylation profile of the promoters may be considered a factor for tumour-specific aberrant expression of the genes.We investigated the methylation status of ...

Multiple myeloma (MM) is an incurable hematological malignancy. Different studies demonstrated the occurrence of genetic and epigenetic alterations in MM. The aberrant methylation is one of the most frequent epigenetic alterations in human genome. This study evaluated the aberrant methylation status of 20 genes in 51 MM samples by quantitative ...

Aberrant DNA methylation is an early event in carcinogenesis and could serve as an additional molecular marker for the early diagnosis. The study was performed to investigate the promoter methylation of DAPK1, CDH13, and TWIST1 genes in uterine cervix lesions in an effort to examine whether this epigenetic event is involved in the process of cervical ...

There is a growing realization that some aging-associated phenotypes/diseases have an epigenetic basis. Here, we report the first genome-scale study of epigenomic dynamics during normal human aging. We identify aging-associated differentially methylated regions (aDMRs) in whole blood in a discovery cohort, and then replicate these aDMRs in sorted CD4⁺ T-cells and ...

The simian virus SV40 (SV40), a potent DNA oncogenic polyomavirus, has been detected in several human tumors including lymphomas, mainly in diffuse large B-cell type (DLBCL). However, a causative role for this virus has not been convincingly established. Hypermethylation in promoter regions is a frequent process of silencing tumor suppressor genes (TSGs) ...

leukemia in Northern California. We measured DNA methylation in the promoter region of the FHIT gene in 190 of the FHIT gene, and methylation in this region correlates with loss of FHIT expression. To test whether aberrant methylation of the FHIT gene may play a role in pediatric leukemia, we assessed the FHIT

We recently discovered that aberrant gene methylation occurs in the stroma and endothelium adjacent to tumor epithelium in prostate cancer patients. This suggests that epigenetic changes such as gene hypermethylation may play a role in the tumor microenvironment. These findings have implications for prostate cancer diagnosis and therpeutic interventions. ...

The relationship of aberrant DNA hypermethylation of cell cycle checkpoint genes with the sensitivity of cancer cells to anticancer drugs is a question of current interest. In this study, we investigated the relationship between aberrant hypermethylation of the CHFR (checkpoint with forkhead-associated and ring ...

It has recently been suggested that silencing of the hMLH1 gene by promoter hypermethylation is the mechanism underlying the presence of the microsatellite instability (MSI) phenotype in sporadic colon and endometrial carcinomas. To determine whether hMLH1 promoter hypermethylation is a relatively early event in ...

The aberrant methylation of promoter CpG islands is known to be a major inactivation mechanism of tumor-related genes, which plays a crucial role in the progression of silencing in human cancers including hepatocellular carcinoma (HCC). Thus, we sought to examine the promoter methylation status of five important DNA damage response ...

Promoter hypermethylation is a marginal approach to inactivating tumor suppressor genes in cancer. DNA hypermethylation is a well-recognized epigenetic malfunction observed in several malignancies, most predominantly in prostate cancer. Aberrant DNA methylation patterns are considered to be the earliest somatic ...

Oral Diseases (2011) Objectives:? Recent studies indicate various molecular abnormalities in oral squamous cell carcinomas (OSCC), including DNA methylation of tumor-associated genes. Although promoter hypermethylation of Wnt pathway antagonists RUNX3 (Runt-related transcription factor 3) and Wnt inhibitory factor 1 (WIF1) has been identified as a common ...

Promoter CpG island hypermethylation has become recognized as an important mechanism for inactivating tumor suppressor genes or tumor-related genes in human cancers of various tissues. Gene inactivation in association with promoter CpG island hypermethylation has been reported to be four times more frequent than ...

DNA methylation patterns are frequently dysregulated in cancer, although little is known of the mechanisms through which specific gene sets become aberrantly methylated. The ecotropic viral integration site 1 (EVI1) locus encodes a DNA binding zinc-finger transcription factor that is aberrantly expressed in a subset of acute myeloid leukemia (AML) patients ...

Aberrant methylation of promoter CpG islands is a hallmark of human cancers and is an early event in carcinogenesis. We examined whether promoter hypermethylation contributes to the pathogenesis of benign breast lesions along a progression continuum to invasive breast cancer. The exploratory study cohort comprised ...

Aberrant methylation of promoter CpG islands is a hallmark of human cancers and is an early event in carcinogenesis. We examined whether promoter hypermethylation contributes to the pathogenesis of benign breast lesions along a progression continuum to invasive breast cancer. The exploratory study cohort comprised ...

The glycoprotein hormone erythropoietin (EPO) is a key regulator in the production of red blood cells. EPO is produced mainly in the embryonic liver and kidney of adults. Other organs are also known to express varying amounts of EPO. In our study, we have analyzed the epigenetic regulation of EPO in human cancer cell lines by DNA methylation assays, chromatin immunoprecipitation, RT-PCR, and ...

RELN (Reelin) is an extracellular glycoprotein that plays a critical role in neuronal migration. Here we show that the RELN gene is frequently silenced in gastric cancers (GCs) by aberrant promoter hypermethylation. Although RELN was strongly expressed in non-tumor gastric epithelia, its expression was weak, or absent, in GC cell lines ...

Ovarian carcinoma (OC) is a leading cause of death among women throughout the world. A number of cancer-associated genes have been shown to be inactivated by hypermethylation of CpG islands during tumorigenesis. We tested the hypothesis that methylation status of MGMT, CDH1, RAR-beta and SYK could be important in the ovarian tumorigenic process and can lead to the gene(s) ...

Aberrant methylation in promoter-associated CpG islands has been recognized as a major mechanism for tumor suppressor gene silencing in several malignancies. We determined the methylation status of nine tumor suppressor genes in 68 newly diagnosed MM patients by methylation-specific PCR. The frequency of promoter ...

Dysregulation of cell cycle control is an important mechanism in carcinogenesis. Gene promoter hypermethylation is an alternative mechanism of gene inactivation. We analyzed the methylation status of the tumor suppressor components of the INK4/Rb pathway in mantle cell lymphoma and follicular lymphoma by methylation-specific polymerase chain reaction for ...

Hypermethylation at the promoter region is an important epigenetic mechanism underlying the inactivation of tumor suppressor genes and frequently occurs as an early event in the development of different types of cancer including colorectal carcinoma (CRC). The aim of the present study is the detection of methylation status for some tumor suppressor genes ...

3p21 is an important locus harbouring critical tumour suppressor genes (TSG), which are implicated in the pathogenesis of multiple tumours, including oesophageal carcinoma. RASSF1A is a 3p21.3 candidate TSG frequently inactivated by promoter methylation in multiple tumours. We investigated RASSF1A promoter methylation and gene expression in Chinese ...

We evaluated promoter hypermethylation of a panel of tumor suppressor genes as a means to detect epigenetic alterations in oral squamous cell carcinomas (OSCC) of Indian-origin and compare with North-American head and neck squamous cell carcinomas (HNSCC). Quantitative-methylation-specific PCR was used to investigate the promoter ...

BackgroundDysfunctioning of CCAAT/enhancer binding protein ? (C/EBP?) in acute myeloid leukemia can be caused, amongst others, by mutations in the encoding gene (CEBPA) and by promoter hypermethylation. CEBPA-mutated acute myeloid leukemia is associated with a favorable outcome, but this may be restricted to the case of double mutations in CEBPA in adult ...

The suppressor of cytokine signaling 3 (SOCS3) gene is one of eight structurally related genes of the SOCS family and has been suggested to function as a tumor suppressor by inhibition of the JAK/STAT signaling pathway. We investigated 60 human gliomas of different histological types for SOCS3 alterations and found frequent SOCS3 promoter hypermethylation ...

Posttranslationally modified histones and DNA hypermethylation frequently interplay to deregulate gene expression in cancer. We report that acute myeloid leukemia (AML) with an aberrant histone methyltransferase, the mixed lineage leukemia partial tandem duplication (MLL-PTD), exhibits increased global DNA methylation versus AML with MLL-wildtype (MLL-WT; ...

Posttranslationally modified histones and DNA hypermethylation frequently interplay to deregulate gene expression in cancer. We report that acute myeloid leukemia (AML) with an aberrant histone methyltransferase, the mixed lineage leukemia partial tandem duplication (MLL-PTD), exhibits increased global DNA methylation versus AML with MLL-wildtype (MLL-WT; ...

The DOK1 gene is a putative tumour suppressor gene located on the human chromosome 2p13 which is frequently rearranged in leukemia and other human tumours. We previously reported that the DOK1 gene can be mutated and its expression down-regulated in human malignancies. However, the mechanism underlying DOK1 silencing remains largely unknown. We show here that unscheduled silencing of DOK1 ...

Aberrant promoter methylation is an important mechanism for gene silencing. In the present study, 50 Barrett's esophagus-associated esophageal adenocarcinomas (ADC), 50 cardiac ADC and 50 gastric ADC were investigated by means of methylation-specific real-time PCR for hypermethylation in the tumor suppressor genes APC, p16(INk4A) and ...

Transcriptional silencing associated with aberrant promoter hypermethylation is a common mechanism of inactivation of tumor suppressor genes in cancer cells. To globally profile the genes silenced by hypermethylation in prostate cancer, we screened a whole genome expression microarray for genes reactivated in the ...

Wilms' tumour (WT) is a pediatric tumor of the kidney that arises via failure of the fetal developmental program. The absence of identifiable mutations in the majority of WTs suggests the frequent involvement of epigenetic aberrations in WT. We therefore conducted a genome-wide analysis of promoter hypermethylation in WTs and ...

Aberrant promoter methylation of the checkpoint gene with forkhead-associated domain and ring finger (CHFR) gene is frequently detected in human cancer. We previously demonstrated that diminished CHFR expression was significantly correlated with both poor prognosis and heavy smoking in nonsmall cell lung cancer (NSCLC). Conversely, epidermal growth ...

BackgroundClaudins are membrane proteins that play critical roles in tight junction (TJ) formation and function. Members of the claudin gene family have been demonstrated to be aberrantly regulated, and to participate in the pathogenesis of various human cancers. In the present study, we report that claudin-11 (CLDN11) is silenced in gastric cancer via ...

BackgroundCancer cells display widespread changes in DNA methylation that may lead to genetic instability by global hypomethylation and aberrant silencing of tumor suppressor genes by focal hypermethylation. In turn, altered DNA methylation patterns have been used to identify putative tumor suppressor genes.MethodsIn a methylation screening approach, we ...

Background: Epstein-Barr virus (EBV)-associated gastric carcinomas (GC) constitute a distinct clinicopathological entity of gastric cancer. In order to determine underlying distinct aberrant promoter methylation we tested cardiac and non-cardiac GC with regard to the presence of EBV.Methods: One hundred GC were tested by RNA-in situ hybridization for the ...

Triple-negative breast cancer (TNBC) occurs in approximately 15% of all breast cancer patients, and the incidence of TNBC is greatly increased in BRCA1 mutation carriers. This study aimed to assess the impact of BRCA1 promoter methylation with respect to breast cancer subtypes in sporadic disease. Tissue microarrays (TMAs) were constructed representing tumors from 303 patients ...

The class III histone deactylase (HDAC), SIRT1, has cancer relevance because it regulates lifespan in multiple organisms, down-regulates p53 function through deacetylation, and is linked to polycomb gene silencing in Drosophila. However, it has not been reported to mediate heterochromatin formation or heritable silencing for endogenous mammalian genes. Herein, we show that SIRT1 localizes to ...

Progressive p16 methylation has been associated with metastasis and invasive phenotypes in many cancers. Loss of E-cadherin (CDH1) function contributes to breast cancer progression by promoting cell proliferation, invasion and metastasis. Using methylation-specific PCR, aberrant hypermethylation of p16 and CDH1 in tumor and plasma was ...

Mantle cell lymphoma (MCL) is a mostly incurable malignancy arising from naive B cells (NBCs) in the mantle zone of lymph nodes. We analyzed genomewide methylation in MCL patients with the HELP (HpaII tiny fragment Enrichment by Ligation�mediated PCR) assay and found significant aberrancy in promoter methylation patterns compared with normal NBCs. Using ...

Methylation profile was analyzed in nine cases of relapsed childhood acute lymphoblastic leukemia (ALL) for p14, p15, p16, Rb, MGMT, APC, hMLH1, RARbeta, RIZ, DAPK, and FHIT genes by using methylation specific polymerase chain reaction (MSP) analysis. Frequency of methylation in each gene was: MGMT, 56%; RARbeta, 44%; and p16, 22%, respectively. None of the p14, p15, Rb, APC, hMLH1, RIZ, DAPK, and ...

Promoter hypermethylation of the p16^INK4a gene was investigated in 81 sets of samples of tumor tissue and adjacent normal tissue from Korean patients with primary lung cancer, using the modified real-time polymerase chain reaction (PCR)/ SYBR Green detection method. The results showed hypermethylation of ...

Cyclin-dependent kinase inhibitors CDKN2B and CDKN2A are tumor suppressor genes that are frequently dysregulated in a variety of cancers. Aberrant regulation via DNA hypermethylation causes gene silencing. Arsenic trioxide has been successfully used to treat malignant, hematopoietic diseases and is known to act by induction of apoptosis and inhibition of ...

Breast Cancer Metastasis Suppressor 1 (BRMS1) suppresses metastasis of human breast cancer, ovarian cancer and melanoma in athymic mice. Studies have also shown that BRMS1 is significantly downregulated in some breast tumors, especially in metastatic disease. However, the mechanisms which regulate BRMS1 expression are currently unknown. Upon examination of the BRMS1 promoter ...

BackgroundAlterations in the DNA methylation pattern are a hallmark of leukemias and lymphomas. However, most epigenetic studies in hematologic neoplasms (HNs) have focused either on the analysis of few candidate genes or many genes and few HN entities, and comprehensive studies are required.Methodology/Principal FindingsHere, we report for the first time a microarray-based DNA methylation study ...

Aberrant hypermethylation of the CpG islands in the promoter region plays a casual role in the inactivation of various key genes involved in the cell cycle regulatory cascade, which could result in loss of cell cycle control. The aim of the present study was to investigate the role of promoter methylation of genes ...

Aberrant hypermethylation of CpG islands in the promoter region plays a causal role in the inactivation of various key genes involved in the cell cycle regulatory cascade, which could result in a loss of cell cycle control. The aim of the present study was to examine in more detail the prevalence and role of the ...

Improvements in epigenetics have resulted in identification of a number of genes with aberrant hypermethylation associated with systematic occurrence of cancer. It is now evident that aberrant hypermethylation inactivates cancer-related genes including those associated with cell cycle control, apoptosis, and DNA ...

It is hard to discriminate myelodysplastic syndrome(MDS) from many benign hematological diseases. To identify the methylation status of zo-1 gene in MDS, the methylation specific PCR (MS-PCR) and reverse transcription-PCR (RT-PCR) were applied to detect the MDS cell line MUTZ-1, bone marrow of a healthy donor and an aplastic anemia patient. MS-PCR was also employed to detect the bone marrow of 72 ...

BackgroundWnt inhibitory factor-1(WIF-1) acts as a Wnt-antagonists and tumor suppressor, but hypermethylation of WIF-1 gene promoter and low expression activate Wnt signaling aberrantly and induce the development of various human tumors. With this work we intended to investigate the expression and promoter ...

Epigenetic events have emerged as key mechanisms in the regulation of critical biological processes and in the development of a wide variety of human malignancies, including gastric cancer (GC), however precise gene targets of aberrant DNA methylation in GC remain largely unknown. Here, we have combined pyrosequencing-based quantitative analysis of DNA methylation in 98 GC ...

... 2) a panel of markers consisting of three genes, Cyclin D2, Twist and retinoic acid receptor 2 (RAR2), which are aberrantly hypermethylated in ...

Aberrant methylation of promoter CpG islands is associated with transcriptional inactivation of tumor-suppressor genes in cancer. TFPI2, a Kunitz-type serine proteinase inhibitor, has been identified as a putative tumor-suppressor gene from genome-wide screening for aberrant methylation, using a microarray combined with the ...

Methylation in the promoter region of many genes is involved in regulating gene expression patterns. Using the Illumina GoldenGate(�) methylation assay, we examined the methylation status of 1505 CpG-sites from 807 genes in 32 samples from patients with acute myeloid leukaemia (AML) at diagnosis, nine at relapse and 15 normal controls and performed additional pyrosequencing ...

A CpG island methylator phenotype (CIMP) is displayed by a distinct subset of colorectal cancers with a high frequency of DNA hypermethylation in a specific group of CpG islands. Recent studies have shown that an activating mutation of BRAF (BRAF^V600E) is tightly associated with CIMP, raising the question of whether BRAF^V600E plays ...

The use of molecular markers in the diagnostics of gliomas aids histopathological diagnosis and allows their further classification into clinically significant subgroups. The aim of this study was to characterize the methylation pattern of the O(6) -methylguanine-DNA methyltransferase (MGMT) promoter, gene copy number aberrations, and isocitrate ...

Although DNA hypermethylation within promoter CpG islands is highly correlated with tumorigenesis, it has not been established whether DNA hypermethylation within a specific tumor suppressor gene (TSG) is sufficient to fully transform a somatic stem cell. In this study, we addressed this question using a novel targeted DNA methylation ...

... Analysis of hypermethylation of other gene promoters in combination has demonstrated high sensitivity and specificity for prostate cancer diagnosis ...

... Analysis of hypermethylation of other gene promoters in combination has demonstrated high sensitivity and specificity for prostate cancer diagnosis ...

Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter occurs in about 40% of breast tumours and has been correlated with reduced APC protein levels. To what extent epigenetic alterations of the APC gene may differ according to specific breast cancer phenotypes, remains to be elucidated. Our aim was to explore the role of APC ...

BackgroundThe prolyl-hydroxylase domain family of enzymes (PHD1-3) plays an important role in the cellular response to hypoxia by negatively regulating HIF-? proteins. Disruption of this process can lead to up-regulation of factors that promote tumorigenesis. We observed decreased basal expression of PHD3 in prostate cancer tissue and tumor cell lines representing diverse ...

BackgroundWnt factors control cell differentiation through semi-independent molecular cascades known as the ?-catenin-dependent (canonical) and -independent (non-canonical) Wnt signalling pathways. Genetic and epigenetic alteration of components of the canonical Wnt signalling pathway is one of the primary mechanisms underlying colon cancer. Despite increasing evidence of the role of the ...

Epigenetic silencing of tumor suppressor genes is a new focus of investigation in the generation and proliferation of carcinomas. Secreted protein acidic and rich in cysteine (SPARC) is reportedly detrimental to the growth of ovarian cancer cells and has been shown to be epigenetically silenced in several cancers. We hypothesized that SPARC is downregulated in ovarian cancer through ...

Transition from malignant schwannoma to malignant triton tumor is analyzed in a case report on a patient with recurring cancers and suspected familial predisposition. It is hypothesized that rhabdomyoblastic differentiation, which distinguishes triton from schwannoma, might be attributable to Hedgehog-Patched pathway malfunctioning. Loss of one Patched gene allele was found in the tissue of ...

Aberrant DNA methylation, in particular promoter hypermethylation and transcriptional silencing of tumor suppressor genes, has an important role in the development of many human cancers, including renal cell carcinoma (RCC). Indeed, apart from mutations in the well studied von Hippel-Lindau gene (VHL), the mutation frequency rates of ...

BackgroundHuman Disabled-2 (DAB2), is a multi-function signalling molecule that it is frequently down-regulated in human cancers. We aimed to investigate the possible tumour suppressor effect of DAB2 in nasopharyngeal carcinoma (NPC).MethodsWe studied the expression of DAB2 in NPC cell lines, xenografts and primary tumour samples. The status of promoter methylation was ...

Increasing evidence shows aberrant hypermethylation of genes occurring in and potentially contributing to pathogenesis of myeloid malignancies. Several of these diseases, such as myelodysplastic syndromes (MDSs), are responsive to DNA methyltransferase inhibitors. To determine the extent of promoter ...

BackgroundAberrant DNA methylation is common in carcinogenesis. The typical pattern appears to involve reduced expression of maintenance DNA methyltransferase, DNMT1, inducing genomic hypomethylation, whereas increased expression of de novo DNMT3a or 3b causes gene-specific hypermethylation.ObjectivesDuring cadmium-induced malignant transformation, an ...

Somatic cell nuclear transfer (SCNT) is an inefficient process, which is due to incomplete reprogramming of the donor nucleus. DNA methylation of imprinted genes is essential to the reprogramming of the somatic cell nucleus in SCNT. Dlk1-Gtl2 imprinted domain has been widely studied in mouse and human. However, little is known in bovine, possibly because of limited appropriate sequences of bovine. ...

The inactivation of tumor-related genes through the aberrant methylation of promoter CpG islands is thought to contribute to tumor initiation and progression. We therefore investigated promoter methylation events involved in cutaneous melanoma by screening 30 genes of interest for evidence of promoter ...

Currently, my primary research focus is in the early detection of prostate cancer using gene-specific promoter region hypermethylation. Gene hypermethylation promises to be a good early detection marker since it is a DNA-based, stable covalent modification of the DNA.

The promoter regions of some genes, in particular tumor suppressor genes, are frequently hypermethylated in cancer, but not normal cells. This methylation is thought to be an early event in carcinogenesis. Through necrosis and apoptosis, tumors release ge...

The promoter regions of some genes, in particular tumor suppressor genes, are frequently hypermethylated in cancer, but not normal cells. We are conducting a nested case-control study (within the NYUWHS cohort) to assess the potential of serum DNA hyperme...

The promoter regions of some genes, in particular tumor suppressor genes, are frequently hypermethylated in cancer, but not normal cells. We are conducting a nested case-control study (within the NYUWHS cohort) to assess the potential of serum DNA hyperme...

Hundreds of genes show aberrant DNA hypermethylation in cancer, yet little is known about the causes of this hypermethylation. We identified RIL as a frequent methylation target in cancer. In search for factors that influence RIL hypermethylation, we found a 12-bp polymorphic sequence around its transcription start ...

Human cancer cells frequently have regions of their DNA hypermethylated, which results in transcriptional silencing of affected genes and promotion of tumor formation. However, it is still unknown whether cancer-associated aberrant DNA methylation is targeted to specific genomic regions, whether this methylation also occurs in ...

BackgroundNumerous hypermethylated genes have been reported in breast cancer, and the silencing of these genes plays an important role in carcinogenesis, tumor progression and diagnosis. These hypermethylated promoters are very rarely found in normal breast. It has been suggested that aberrant ...

BackgroundAberrant DNA methylation of CpG islands of cancer-related genes is among the earliest and most frequent alterations in cancerogenesis and might be of value for either diagnosing cancer or evaluating recurrent disease. This mechanism usually leads to inactivation of tumour-suppressor genes. We have designed the current study to validate our previous microarray data ...

Aberrant methylation of tumor suppressor genes (TSG) is an important epigenetic event in cancer, including multiple myeloma (MM). Interleukin-6 (IL-6), which plays a significant role in the pathogenesis of MM, also regulates DNA methylation. However, attempts to bring IL-6 blockade to the clinic have had limited success. We hypothesize that IL-6 regulation of ...

Adenomyosis is a fairly common gynecologic disease with unknown pathogenesis. We sought to investigate as to whether the promoter of progesterone receptor isoform B (PR-B) is hypermethylated in adenomyosis and to investigate the treatment of ectopic endometrial stromal cells with trichostatin A (TSA), a histone deacetylase inhibitor (HDI), and ...

OBJECTIVEPromoter hypermethylation is emerging as a promising molecular strategy for early detection of cancer. We examined promoter methylation status of 1,143 cancer-associated genes to perform a global but unbiased inspection of methylated regions in head and neck squamous cell carcinoma (HNSCC).STUDY DESIGNA laboratory-based study.SETTINGIntegrated ...

The aim of this study was to determine p16 gene mutation, deletion, and promoter 5' CpG island hypermethylation in peripheral blood mononuclear leukocyte of patients with arseniasis as attributed to exposure to indoor unventilated coal stove. The role of the aberrant change of p16 gene in the induction and development of carcinogenesis ...

In the course of gastric cancer development, gene silencing by DNA hypermethylation is an important mechanism. While DNA methylation often co-exists with histone modifications to regulate gene expression, the function of histone modifications in gene silencing in gastric cancer has not been evaluated in detail. p16, a well-known tumor suppressor gene, is frequently silenced in ...

The development and progression of colorectal cancer (CRC) is a multi-step process, and the Wnt pathways with its two molecular gladiators adenomatous polyposis coli (APC) and ?-catenin plays an important role in transforming a normal tissue into a malignant one. In this study, we aimed to investigate the role of aberrations in the APC and ?-catenin genes in the pathogenesis ...

The p16^INK4a (p16) tumor suppressor gene can be inactivated by promoter region hypermethylation in many tumor types including lung cancer, the leading cause of cancer-related deaths in the U.S. We have determined the timing of this event in an animal model of lung carcinogenesis and in human squamous cell carcinomas (SCCs). In the ...

Many genes undergo aberrant methylation in human cancers, and microarray platforms enable more comprehensive profiling of aberrant DNA methylation patterns.Results1,010 of 87,922 probes on the 88 K promoter array (606 genes) had a higher signal (log₂ > 2) in the pancreatic cancer line, Panc-1 compared to the ...

Aberrant promoter hypermethylation is frequently observed in cancer. The potential for this mechanism to contribute to tumor development depends on whether the genes affected are repressed because of their methylation. Many aberrantly methylated genes play important roles in development and are bivalently marked in ...

Aberrant promoter hypermethylation is frequently observed in cancer. The potential for this mechanism to contribute to tumor development depends on whether the genes affected are repressed because of their methylation. Many aberrantly methylated genes play important roles in development and are bivalently marked in ...

Aberrant hypermethylation of gene promoter regions is one of the mechanisms for inactivation of tumour suppressor genes in many human cancers including breast carcinoma. In the current study, we aimed to assess by MSP, the methylation pattern of two cancer-related genes involved in DNA repair: hMLH1 (mutL homolog 1, colon cancer, ...

Tachykinin-1 (TAC1) is the precursor protein for neuroendocrine peptides, including substance P, and is centrally involved in gastric secretion, motility, mucosal immunity, and cell proliferation. Here we report aberrant silencing of TAC1 in gastric cancer (GC) by promoter hypermethylation. TAC1 methylation and mRNA expression in 47 ...

Promoter hypermethylation has been shown to be a common mechanism for inactivation of tumor suppressor genes in breast cancer. The aim of this study was to investigate the prevalence of Slit2 promoter hypermethylation in both the tumor and serum samples of breast cancer patients with ductal carcinoma in situ (DCIS) ...

Multiple genetic and epigenetic alterations are known to be involved in the carcinogenesis of peripheral pulmonary adenocarcinoma (ADC). However, epigenetic abnormalities have not been extensively investigated in the following multistage progression sequence: atypical adenomatous hyperplasia (AAH) to adenocarcinoma in situ (AIS), to invasive ADC. To determine the potential role of ...

Aberrant methylation of promoter CpG islands in human genes represents an alternative mechanism for genetic inactivation, and contributes to the development of human tumors. Nevertheless, thus far, few reports have analyzed methylation in ependymomas. We determined the frequency of aberrant CpG island methylation of several ...

An important pathway of gene transcriptional inactivation is hypermethylation at the CpG islands of promoter regions. Some tumor suppressor genes have been reported to harbor promoter hypermethylation in head and neck cancer. We studied DNA hypermethylation of 4 genes in 42 cases of primary ...

Aberrant activation of Wnt pathways is a common feature of many types of human malignancies. Several studies have demonstrated that the genes encoding secreted Wnt antagonists are frequently silenced in tumor cells by hypermethylation, consistent with the idea that these proteins often function as tumor suppressors. Members of the secreted Frizzled-related ...

BACKGROUND: Bisphenol A (BPA) is an estrogenic endocrine disruptor commonly used in manufacture of polycarbonate plastics and epoxy resins. Due to its ubiquitous presence in the environment, health concerns are increasing. Earlier studies from our group have shown that neonatal exposure of male rats to BPA affected spermatogenesis leading to impairment in fertility during adulthood. Further we ...

Aberrant DNA methylation (DNAm) was first linked to cancer over 25 yr ago. Since then, many studies have associated hypermethylation of tumor suppressor genes and hypomethylation of oncogenes to the tumorigenic process. However, most of these studies have been limited to the analysis of promoters and CpG islands (CGIs). Recently, new ...

Aberrant DNA methylation (DNAm) was first linked to cancer over 25 yr ago. Since then, many studies have associated hypermethylation of tumor suppressor genes and hypomethylation of oncogenes to the tumorigenic process. However, most of these studies have been limited to the analysis of promoters and CpG islands (CGIs). Recently, new ...

The aberrant methylation of cytosine residues in the promoter region of growth regulatory genes is now widely recognized as an additional mechanism for gene inactivation in cancer cells. In this study we analyzed the methylation status of four growth regulatory genes (p16, RASSF1A, cyclinD2, 14-3-3?) during breast cancer progression. For this purpose ...

The aberrant changes of tumor suppressor genes (TSGs) are now recognized as an important mechanism contributing to the development of acute myeloid leukemia (AML). CCAAT/enhancer binding protein zeta (C/EBP?), a candidate TSG, has been found to be involved in cancers including AML. We detected the methylation status of C/EBP? promoter in 133 patients with ...

... A new area of interest has been ... characteristics and promoter hypermethylation detection status for ... Age PSA (μg/ml) DRE Clinical Stage Gleason ...

... ABSTRACT This proposal was initially based on the IDEA award concept that the abnormal gene promoter DNA methylation status of the AP2 gene ...

... Abstract : This proposal was initially based on the IDEA award concept that the abnormal gene promoter DNA methylation status of the AP2 gene ...

... The promoter regions of some genes, in particular tumor suppressor genes, are frequently ... DNA methylation analysis requires two basic steps. ...

Modern neuropathology serves a key function in the multidisciplinary management of brain tumor patients. Owing to the recent advancements in molecular neurooncology, the neuropathological assessment of brain tumors is no longer restricted to provide information on a tumor�s histological type and malignancy grade, but may be complemented by a growing number of molecular tests for clinically ...

SummaryHuman cancer genomes are characterized by widespread aberrations in DNA methylation patterns including DNA hypomethylation of mostly repetitive sequences and hypermethylation of numerous CpG islands. The analysis of DNA methylation patterns in cancer has progressed from single gene studies examining potentially important candidate genes to a more ...

Aberrant DNA methylation participates in carcinogenesis and is a molecular hallmark of a tumor cell. Tumor cells generally exhibit a redistribution of DNA methylation resulting in global hypomethylation with regional hypermethylation; however, the speed in which these changes emerge has not been fully elucidated and may depend on the temporal location of ...

Aberrant DNA methylation participates in carcinogenesis and is a molecular hallmark of a tumor cell. Tumor cells generally exhibit a redistribution of DNA methylation resulting in global hypomethylation with regional hypermethylation; however, the speed in which these changes emerge has not been fully elucidated and may depend on the temporal location of ...

Prostate cancer is the most common malignancy of the urogenital tract. Although controversial, prostate-specific antigen (PSA) testing is widely used for screening and follow-up of prostate cancer, but because of its limited specificity and sensitivity, PSA is not an ideal test. We currently lack the necessary tools to differentiate between latent disease with little likelihood of clinical ...

The bladder cancer genome harbors numerous oncogenic mutations and aberrantly methylated gene promoters. The aim of our study was to generate a profile of these alterations and investigate their use as biomarkers in urine sediments for noninvasive detection of bladder cancer. We systematically screened FGFR3, PIK3CA, TP53, HRAS, NRAS and KRAS for mutations ...

BackgroundSquamous cell carcinoma of esophagus (SCCE) occurs at a high incidence rate in certain parts of the world. This feature necessitates that different aspects of the disease and in particular genetic characteristics be investigated in such regions. In addition, such investigations might lead to achievement of molecular markers helpful for early detection, successful treatment and follow up ...

Epigenetic changes are considered to be a frequent event during tumour development. Hypermethylation of promoter CpG islands represents an alternative mechanism to inactivate tumour suppressor genes, DNA repair genes, cell cycle regulators and transcription factors. In search of epigenetic events related to progression, we used MS-MLPA (ME-0002-B1, ...

Aberrant activation of canonical Wnt signaling is a hallmark event in colorectal carcinogenesis. The Dickkopf-1 (DKK1) and Secreted Frizzled Related Protein 1 (SFRP1) genes encode extracellular inhibitors of Wnt signaling that are frequently silenced by promoter hypermethylation in colorectal cancer (CRC). These methylation events have ...

Silencing of tumor suppressor genes plays a vital role in head and neck carcinogenesis. In this study, we aimed to evaluate to the utility of aberrant promoter hypermethylation for detection in a panel of 10 genes (KIF1A, EDNRB, CDH4, TERT, CD44, NISCH, PAK3, VGF, MAL and FKBP4) in head and neck squamous cell carcinoma (HNSCC) via a ...

Silencing of tumor suppressor genes plays a vital role in head and neck carcinogenesis. In this study, we aimed to evaluate to the utility of aberrant promoter hypermethylation for detection in a panel of 10 genes (KIF1A, EDNRB, CDH4, TERT, CD44, NISCH, PAK3, VGF, MAL and FKBP4) in head and neck squamous cell carcinoma (HNSCC) via a ...

Using methylation-specific real-time PCR, we determined the prevalence of aberrant methylation in the mismatch repair gene hMLH1 and in the recently described HPP1 gene among 50 esophageal, 50 cardiac and 50 gastric ADCs. Additionally, expression of hMLH1 protein was detected immunohistochemically and correlated with DNA MSI. Hypermethylation of hMLH1 was ...

BackgroundHepatocellular carcinoma (HCC), one of the most common cancers world-wide occurs twice as often in men compared to women. Predisposing conditions such as alcoholism, chronic viral hepatitis, aflatoxin B1 ingestion, and cirrhosis all contribute to the development of HCC.MethodsWe used a combination of methylation specific PCR and bisulfite sequencing, qReal-Time PCR (qPCR), and Western ...

Nicotinic acetylcholine receptor (nAChR) genes form a highly conserved gene cluster at the lung cancer susceptibility locus 15q25.1. In this study, we show that the CHRN ? 3 gene encoding nAChR ? 3 subunit is a frequent target of aberrant DNA hypermethylation and silencing in lung cancer, whereas the adjacent CHRN ? 4 and CHRN ? 5 genes exhibit moderate ...

BackgroundAberrant hypermethylation of CpG islands in housekeeping gene promoters and widespread genome hypomethylation are typical events occurring in cancer cells. The molecular mechanisms behind these cancer-related changes in DNA methylation patterns are not well understood. Two questions are particularly important: (i) how are CpG ...

Recent studies have highlighted the histone H3K4 methylation (H3K4me)-dependent transcriptional repression in Saccharomyces cerevisiae; however, the underlying mechanism remains inexplicit. Here, we report that H3K4me inhibits the basal PHO5 transcription under high-phosphate conditions by suppressing nucleosome disassembly at the promoter. We found that derepression of the ...

BackgroundAbnormal germline DNA methylation in males has been proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. Previous studies have been focused on imprinted genes with DNA methylation in poor quality human sperms. However, recent but limited data have revealed that sperm methylation abnormalities may involve large numbers ...

Aberrant promoter hypermethylation is one of the major mechanisms in carcinogenesis and some critical growth regulatory genes have shown commonality in methylation across solid tumors. Twenty-six genes, 14 identified through methylation in colon and breast cancers, were evaluated using primary lung adenocarcinomas (n = 175) from ...

PurposeAberrant promoter hypermethylation of tumor suppressor genes is a promising marker for lung cancer detection. We investigated the likelihood of detecting aberrant DNA methylation of tumor suppressor genes, in plasma samples of patients with abnormalities of the lung detected upon CT-scan.Experimental ...

The role of epigenetics and significance of aberrant gene regulation in etiology of cancer is a well-established phenomenon. The hallmark of cancer epigenetics is aberrant DNA methylation consisting of global hypomethylation and regional hypermethylation of tumor suppressor genes (TSGs) by DNA methyltransferases (DNMTs). In mammals, ...

Members of the Gadd45 family play central roles in the cellular response to genotoxic stress and have been implicated in several human cancers, including hepatocellular carcinomas. Chronic infection by hepatitis C virus (HCV) is a major risk factor for the onset and development of primary hepatocellular tumors, although the underlying mechanisms are unclear. Here, we show a novel link between ...

Members of the Gadd45 family play central roles in the cellular response to genotoxic stress, and have been implicated in several human cancers including hepatocellular carcinomas. Chronic infection by hepatitis C virus (HCV) is a major risk factor for the onset and development of primary hepatocellular tumors, although the underlying mechanisms are unclear. Here, we demonstrate a novel link ...

BackgroundNeuroblastoma, a cancer derived from precursor cells of the sympathetic nervous system, is a major cause of childhood cancer related deaths. The single most important prognostic indicator of poor clinical outcome in this disease is genomic amplification of MYCN, a member of a family of oncogenic transcription factors.MethodologyWe applied MYCN chromatin immunoprecipitation to microarrays ...

Maintaining and acquiring the pluripotent cell state in plants is critical to tissue regeneration and vegetative multiplication. Histone-based epigenetic mechanisms are important for regulating this undifferentiated state. Here we report the use of genetic and pharmacological experimental approaches to show that Arabidopsis cell suspensions and calluses specifically repress some genes as a result ...

MicroRNAs (miRNAs) are recognized as being central players in many biological processes and cellular pathways. Their roles in disease have been highlighted first by observation of their aberrant expression profiles in human tumors, and then by in vitro and in vivo functional studies in transformed cells and model organisms. One of the most commonly observed features of miRNAs ...

BackgroundEpigenetic silencing of tumor suppressor genes play important roles in NPC tumorgenesis. Tissue factor pathway inhibitor-2 (TFPI-2), is a protease inhibitor. Recently, TFPI-2 was suggested to be a tumor suppressor gene involved in tumorigenesis and metastasis in some cancers. In this study, we investigated whether TFPI-2 was inactivated epigenetically in nasopharyngeal carcinoma ...

Glioblastoma (GBM) is an aggressive and lethal cancer, accounting for the majority of primary brain tumors in adults. GBMs are characterized by large and small alterations in genes that control cell growth, apoptosis, angiogenesis, and invasion. Epigenetic alterations also affect the expression of cancer genes, either alone or in combination with genetic mechanisms. The current evidence suggests ...

Although the bcr-abl translocation has been shown to be the causative genetic aberration in chronic myeloid leukemia (CML), there is mounting evidence that the deregulation of other genes, such as the transcription factor interferon regulatory factor 4 (IRF-4), is also implicated in the pathogenesis of CML. Promoter methylation of CpG target sites or ...

Epigenetic mechanisms such as DNA methylation and histone modifications drive stable, clonally propagated changes in genes expression and can therefore serve as molecular mediators of pathway dysfunction in neoplasia. MDS is characterized by frequent epigenetic abnormalities, including the hypermethylation of genes that control proliferation, adhesion, and other characteristic ...

Aberrant methylation of tumor suppressor genes can lead to their silencing in many cancers. TSC-22 is a gene silenced in several solid tumors, but its function and the mechanism(s) responsible for its silencing are largely unknown. Here we demonstrate that the TSC-22 promoter is methylated in primary mouse T or natural killer (NK) large granular lymphocyte ...

Methylation of CpG islands is associated with transcriptional repression and, in cancer, leads to the abnormal silencing of tumor suppressor genes. We have developed a novel technique for detecting CpG-methylated DNA termed methyl-binding (MB)-PCR. This technique utilizes a recombinant protein with high affinity for CpG-methylated DNA that is coated onto the walls of a PCR vessel and selectively ...

Drug-induced liver injury, including drug-induced hepatotoxicity during the treatment of tuberculosis infection, is a major health problem with increasingly significant challenges to modern hepatology. Therefore, the assessment and monitoring of the hepatotoxicity of antituberculosis drugs for prevention of liver injury are great concerns during disease treatment. The recently emerged data showing ...

To investigate whether alterations in histone modifications occur in esophageal squamous cell carcinoma (ESCC), we measured histone H3/ H4 acetylation and H3K4/H3K27 methylation levels, as well as the expression of chromatin modifier genes in tumor and healthy esophageal tissue from ESCC patients. We found evidence of global H3 and H4 hypoacetylation, H3K4 and H3K27 ...

Alterations of the retinoblastoma (RB1) tumor suppressor gene are not only associated with retinoblastoma but also with several other malignancies including osteosarcoma. Besides direct sequence alterations, hypermethylation of a CpG island in the promoter region can cause inactivation of the RB1 gene as it has been shown in retinoblastomas. We examined ...

Oral squamous cell carcinoma (OSCC) is characterized by high mortality rates. High incidence of local recurrences in the normal-appearing surgical margins of OSCC patients indicates the existence molecular alterations, including DNA methylation, which could not be detectable by histopathologic analysis. The objective of our study was to determine correlation of tumor-related genes ...

BACKGROUND: Cervical cancer is a leading cause of cancer related deaths in women worldwide caused due to infection of high-risk human papillomaviruses. As JAK/STAT signalling pathway has been shown to play an important role during carcinogenesis, we studied the role of silencing of Suppressor of Cytokine Signalling-1 (SOCS-1) gene, a negative regulator of JAK/STAT pathway in cervical cancer. ...

The microRNA (miRNA) genes mir-127 and mir-136 are located near two CpG islands in the imprinted mouse retrotransposon-like gene Rtl1, a key gene involved in placenta formation. These miRNAs appear to be involved in regulating the imprinting of Rtl1. To obtain insights into the epigenetic reprogramming of cloned embryos, we compared the expression levels of mir-127 and mir-136 in fertilized mouse ...

It is well established that aberrant gene regulation by epigenetic mechanisms can develop as a result of pathological processes such as cancer. Methylation of CpG islands is an important component of the epigenetic code and a number of genes become abnormally methylated during tumorigenesis. Some bioactive food components have been shown to have cancer inhibition activities by ...

It is well established that aberrant gene regulation by epigenetic mechanisms can develop as a result of pathological processes such as cancer. Methylation of CpG islands is an important component of the epigenetic code and a number of genes become abnormally methylated during tumorigenesis. Some bioactive food components have been shown to have cancer inhibition activities by ...

ZAC is a paternally expressed, imprinted gene located on chromosome 6q24, within a region known to harbor a tumor suppressor gene for several types of neoplasia, including human ovarian cancer (HOC). We have failed to identify genetic mutations in the ZAC gene in tumor material. Many imprinted genes contain differentially allele-specific-methylated regions (DMR) and harbor ...

Recent studies have shown aberrant expression of SOX11 in various types of aggressive B-cell neoplasms. To elucidate the molecular mechanisms leading to such deregulation, we performed a comprehensive SOX11 gene expression and epigenetic study in stem cells, normal hematopoietic cells and different lymphoid neoplasms. We observed that SOX11 expression is associated with ...

Recent studies have shown aberrant expression of SOX11 in various types of aggressive B-cell neoplasms. To elucidate the molecular mechanisms leading to such deregulation, we performed a comprehensive SOX11 gene expression and epigenetic study in stem cells, normal hematopoietic cells and different lymphoid neoplasms. We observed that SOX11 expression is associated with ...

Genetic amplification, mutation, and translocation are known to play a causal role in the up-regulation of an oncogene in cancer cells. Here we report an emerging role of microRNA, the epigenetic deregulation of which may also lead to this oncogenic activation. SOX4, an oncogene belonging to the SRY-related high-mobility-group-box family, was found to be over-expressed (P<0.005) in endometrial ...

Aberrant promoter hypermethylation of cancer associated genes occur frequently during carcinogenesis and may serve as a cancer biomarker. The aim of this study was to investigate the occurrence and relevance of promoter methylation of the tumor suppressor DAPK-1, APAF-1 () and SPARC in relation to different ...

ObjectiveHypermethylation of CpG island is a common mechanism for the inactivation of tumor suppressor genes. Hypermethylation of the E-cadherin promoter region has been rarely studied in endometrial carcinoma of Korean women. The purpose of this study is to investigate methylation status of E-cadherin promoter ...

Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding the delayed, non-targeted effects of radiation including radiationinduced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic ...

CpG island hypermethylation is frequently found during gastric carcinogenesis. We investigated methylation profiles of p16, LOX, HAND1, THBD, p41ARC, and APC along multistep gastric carcinogenesis and determined their association with Helicobacter pylori infection. Methylation levels in these six genes were evaluated in noncancerous gastric biopsy specimens using quantitative ...

Background-Sporadic breast cancer like many other cancers is proposed to be a manifestation of abnormal genetic and epigenetic changes. For the past decade our laboratory has identified genes involved in DNA damage response (DDR), apoptosis and immunesurvelliance pathways to influence sporadic breast cancer risk in north Indian population. Further to enhance our knowledge at the epigenetic level, ...

P16(Ink4a) is an important factor in carcinogenesis and its expression can be linked to oncogene-induced senescence. Oncogene-induced senescence is characterized by growth arrest and occurs as a consequence of oncogene activation due to KRAS or BRAF mutation. It has been shown that the induction of p16(Ink4a) in premalignant lesions and its loss during malignant transformation is an important ...

Because existing surgical and management methods can consistently cure only early-stage ovarian cancer, novel strategies for early detection are required. Silencing of tumor suppressor genes such as p16INK4a, VHL, and hMLH1 have established promoter hypermethylation as a common mechanism for tumor suppressor inactivation in human cancer and as a promising ...

The hepatitis B virus�protein (HBx) has been implicated as a potential trigger of the epigenetic deregulation of some genes, but the underlying mechanism remains unknown. The aim of this study is to identify underlying mechanisms involved in HBx-mediated epigenetic modification in the process of HBx induced p16(INK4A) promoter hypermethylation. Liver ...

CpG island arrays represent a high-throughput epigenomic discovery platform to identify global disease-specific promoter hypermethylation candidates along bladder cancer progression. DNA obtained from 10 pairs of invasive bladder tumours were profiled vs their respective normal urothelium using differential methylation hybridisation on custom-made CpG ...

The hypermethylation of the CpG islands is a common mechanism for the inactivation of tumor-related genes. In the present study, we analyzed the methylation status of genes for cell repair such as hMLH1, MGMT, and GSTP1, and a gastric cancer-specifically methylated DNA fragment, MINT 25 in gastric cancer cases and control groups. The study population consisted of 100 gastric ...

PurposeRUNX3 is a known tumor suppressor gene in several carcinomas. Aberration in RUNX3 expression has not been described for cutaneous melanoma. Therefore, we assessed the expression of RUNX3 in cutaneous melanoma andits regulatory mechanisms relative to tumor progression.Experimental DesignThe expression of RUNX3 mRNA and miR-532-5p (microRNA) was assessed in melanoma lines ...

BackgroundCisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, resulting in fully chemoresistant, fatal disease. Although the precise mechanism(s) underlying the development of platinum resistance in late-stage ovarian cancer patients ...

AbstractChronic gastroesophageal reflux disease is a known risk factor for Barrett's esophagus (BE), that induces oxidative mucosal damage. Glutathione peroxidase-3 (GPx3) is a secretory protein with potent extracellular antioxidant activity. Herein, we have investigated the mRNA and protein expression of GPx3, and explored promoter hypermethylation as an ...

This proposal was initially based on the IDEA award concept that the abnormal gene promoter DNA methylation status of the AP2 gene might predict which DCIS lesions in women would be at risk for the evolution of recurrence and/or emergence of invasive canc...

Hypermethylation of tumor suppressor genes is only thought to occur in the somatic cell in sporadic tumors. However, we propose that methylation of the promoter of tumor suppressor genes, such as BRCA1, may also occur in the germ-line. Germ-line inheritan...

Aberrant DNA hypermethylation of tumor suppressor genes is thought to be an early event in tumorigenesis. Many studies have reported the methylation status of individual genes with known involvement in cancer, but an unbiased assessment of the biological function of the collective of hypermethylated genes has not been conducted so far. ...

Gene silencing by aberrant epigenetic chromatin alteration is a well-recognized event contributing to tumorigenesis. While genetically engineered tumor-prone mouse models have proven a powerful tool in understanding many aspects of carcinogenesis, to date few studies have focused on epigenetic alterations in mouse tumors. To uncover epigenetically silenced tumor suppressor ...

BackgroundHomeobox genes murine Rhox5 and human RHOXF1 are expressed in early embryonic stages and then mostly restricted to germline tissues in normal adult, yet they are aberrantly expressed in cancer cells in vitro and in vivo . Here we study the epigenetic regulation and potential functions of Rhox5 gene.FindingsIn Rhox5 -silenced or extremely low expresser cells, we ...

Fragile X syndrome (FXS) is an X-linked condition associated with intellectual disability and behavioral problems. It is caused by expansion of a CGG repeat in the 5' untranslated region of the fragile X mental retardation 1 (FMR1) gene. This mutation is associated with hypermethylation at the FMR1 promoter and resultant transcriptional silencing. FMR1 ...

Metastatic melanoma is a fatal disease due to the lack of successful therapies and biomarkers for early detection and its incidence has been increasing. Genetic studies have defined recurrent chromosomal aberrations, suggesting the location of either tumor suppressor genes or oncogenes. Transcription factor 21 (TCF21) belongs to the class A of the basic helix-loop-helix family ...

ObjectiveDNA promoter methylation is an epigenetic phenomenon for long-term gene silencing during tumorigenesis. The purpose of this study is to identify novel hypermethylated loci associated with clinicopathologic variables in endometrioid endometrial carcinomas.MethodsTo find hypermethylated promoter loci, we ...

Hypermethylation of the O6-MGMT, p14ARF, p16INK4a, RASSF1A and APC1A genes are unfavourable prognostic markers in colorectal cancer (CRC). We hypothesized that they could be related to prognosis also in cervical cancer. Methylation was studied in DNA extracts from surgical specimens of cancer tissue by novel pyrosequencing methods. In 109 patients (90 squamous cell carcinomas, ...

We recently analyzed the hypermethylation status of the p16INK4a (p16) gene promoter in normal-appearing mucosa obtained from patients with colorectal cancer. Hypermethylation of p16 was associated with reduced survival of these patients. In the present study, germ line polymorphisms in the folate- and methyl-associated genes, ...

AIM: To investigate the feasibility of detecting hypermethylated secreted frizzled-related protein 2 (SFRP2) gene in fecal DNA as a non-invasive screening tool for colorectal cancer (CRC).METHODS: Fluorescence-based real-time PCR assay (MethyLight) was performed to analyze SFRP2 gene promoter methylation status in a blinded fashion in tumor tissues and in ...

Aberrant DNA methylation and miRNA expression play important roles in the pathogenesis of pancreatic cancer. While interrogating differentially methylated CpG islands in pancreatic cancer we identified two members of miR-200 family, miR-200a and miR-200b that were hypomethylated and overexpressed in pancreatic cancer. We also identified prevalent ...

Aberrant DNA methylation is common in carcinogenesis. The typical pattern appears to involve reduced expression of maintenance DNA methyltransferase, DNMT1, inducing genomic hypomethylation, whereas increased expression of de novo DNMT3a or 3b causes gene-specific hypermethylation. During cadmium-in...

Hypermethylation of the MGMT gene promoter and mutation of the TP53 tumor-suppressor gene are frequently present in diffuse astrocytomas. However, there is only anecdotal information about MGMT methylation status and TP53 mutations during progression of low-grade diffuse astrocytoma (AII) to anaplastic astrocytoma (AIII) and secondary glioblastoma (sGB). ...

Gene expression-based prediction of genomic copy number aberrations in the chromosomal region 12q13 to 12q15 that is flanked by MDM2 and CDK4 identified Wnt inhibitory factor 1 (WIF1) as a candidate tumor suppressor gene in glioblastoma. WIF1 encodes a secreted Wnt antagonist and was strongly downregulated in most glioblastomas as compared with normal brain, implying ...

Genome wide hypomethylation and regional hypermethylation of cancer cells and tissues remain a paradox, though it has received a convincing confirmation that epigenetic switching systems, including DNA-methylation represent a fundamental regulatory mechanism that has an impact on genome maintenance and gene transcription. Methylated cytosine residues of vertebrate DNA are ...

Although a number of molecular aberrations have been described in acute myeloid leukaemia (AML), no study has yet determined their relative prognostic importance. We have analysed blast cells from 250 adult patients treated at the same institution during a 15-year period. Balanced translocations were detected by multiplex polymerase chain reaction in 13% of the cases. Internal ...

BackgroundPrevious studies have shown that the expression of tissue factor pathway inhibitor-2 (TFPI-2), a matrix-associated Kunitz-type serine proteinase inhibitor, is markedly down-regulated in several tumor cells through hypermethylation of the TFPI-2 gene promoter. In the present study, RT-PCR analysis of total RNA from both human normal and tumor ...

Thyroid cancer is the most common endocrine cancer with 1,690 deaths each year. There are four main types of which the papillary and follicular types together account for >90% followed by medullary cancers with 3% to 5% and anaplastic carcinomas making up <3%. Epigenetic events of DNA hypermethylation are emerging as promising molecular targets for cancer detection. Our ...

Epigenetic inactivation due to aberrant promoter methylation is a key process in breast tumorigenesis. Murine models for human breast cancer have been established for nearly every important human oncogene or tumor suppressor gene. Mouse-to-human comparative gene expression and cytogenetic profiling have been widely investigated for these models; however, ...

DNA and histone methylation are epigenetic modifications functioning in transcriptional control and have been implicated in the deregulation of gene expression in cancer. As a first step to determine if histone methylation could be involved in testis cancer pathogenesis, we performed immunofluorescent localization of histone H3 methylation at lysine 4 (H3-K4; gene activating) and lysine 9 (H3-K9; ...

Early exposure to xenoestrogens may predispose to breast cancer risk later in adult life. It is likely that long-lived, self-regenerating epithelial progenitor cells are more susceptible to these exposure injuries over time and transmit the injured memory through epigenetic mechanisms to their differentiated progeny. Here, we used progenitor-containing mammospheres as an in vitro exposure model to ...

Epigenetic silencing involving the aberrant DNA methylation of promoter-associated CpG islands is one mechanism leading to the inactivation of tumor suppressor genes in human cancers. However, the molecular mechanisms underlying this event remains poorly understood. TMS1/ASC is a novel proapoptotic signaling factor that is subject to epigenetic ...

Worldwide oral squamous cell carcinoma (OSCC) accounts for more than 100,000 deaths each year. Chronic inflammation constitutes one of the key risk factors for OSCC. Accumulating evidence suggests that aberrant DNA methylation may contribute to OSCC tumorigenesis. This study investigated whether chronic inflammation alters DNA methylation and expression of cancer-associated ...

Worldwide oral squamous cell carcinoma (OSCC) accounts for more than 100,000 deaths each year. Chronic inflammation constitutes one of the key risk factors for OSCC. Accumulating evidence suggests that aberrant DNA methylation may contribute to OSCC tumorigenesis. This study investigated whether chronic inflammation alters DNA methylation and expression of cancer-associated ...

The DNA hypomethylating drug decitabine maintains normal hematopoietic stem cell (HSC) self-renewal but induces terminal differentiation in acute myeloid leukemia (AML) cells. The basis for these contrasting cell fates, and for selective CpG hypomethylation by decitabine, is poorly understood. Promoter CpGs, with methylation measured by microarray, were classified by the ...

Aberrant methylation of promoter CpG islands is causally linked with a number of inherited syndromes and most sporadic cancers, and may provide valuable diagnostic and prognostic biomarkers. In this report, we describe an approach to simultaneous analysis of multiple CpG islands, where methylation-specific oligonucleotide probes are joined by ligation and ...

Glioblastoma Multiforme (GBM), the most common and lethal primary human brain tumor, exhibits multiple molecular aberrations. We report that loss of the transcription factor GATA4, a negative regulator of normal astrocyte proliferation, is a driver in glioma formation and fulfills the hallmarks of a tumor suppressor gene (TSG). Although GATA4 was expressed in normal brain, ...

The downregulation of specific genes through DNA hypermethylation is a major hallmark of cancer, although the extent and genomic distribution of hypermethylation occurring within cancer genomes is poorly understood. We report on the first genome-wide analysis of DNA methylation alterations in different neuroblastic tumor subtypes and cell lines, revealing ...

Many human genes exhibit evidence of initiated RNA polymerase II (Pol II) at their promoters, despite a lack of significant full-length transcript. Such genes exhibit promoter-proximal �pausing,� wherein initiated Pol II accumulates just downstream of the transcription start site due to a rate-limiting step mediating the transition to elongation. The ...

Plant genomic DNA methylation was analyzed by an improved SssI methyltransferase assay and by genomic sequencing with sodium bisulfite. Kanamycin, hygromycin, and cefotaxime (also called Claforan) are commonly used as selective agents for the production of transgenic plants. These antibiotics caused DNA hypermethylation in tobacco plants grown in vitro, which was both time- ...

The tumor-suppressor gene PTEN/MMAC1, on chromosome 10q23.3, has been implicated in an important number of human tumors, such as thyroid carcinomas. PTEN somatic mutations occur in sporadic tumors of the endometrium, brain, prostate, or melanomas, while germline mutations predispose to development of the multiple hamartoma syndromes (i.e., Cowden's disease and Bannayan-Zonana syndrome). Activation ...