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PubMedDate not supplied

Aberrant promoter hypermethylation of multiple genes in head and neck squamous cell carcinoma.

PURPOSE: Epigenetic alteration, via promoter hypermethylation, inactivates genes important for the development of head and neck squamous cell carcinoma (SCCHN). The aim of this study is to characterize and correlate, with clinical parameters, the promoter methylation profile of DNA repair genes, hMLH1 and O6-methylguanine-DNA methyltransferase (MGMT), and tumor-suppressor gene p16. MATERIALS AND METHODS: Fifty-one cases of SCCHN, collected from the paraffin block archives (1997-1999) in the Department of Pathology at the University of Arkansas for medical sciences, provided DNA for methylation-specific PCR using primers specific for hMLH1, MGMT, and p16. RESULTS: Sixty-two percent displayed promoter hypermethylation in at least one gene, with 23% seen for hMLH1, 30% for MGMT, and 36% for p16. Promoter hypermethylation of these genes separately or in combination was not associated with history of smoking and alcohol use, tumor size, nodal status, clinical stage, and overall survival. Promoter hypermethylation of more than 1 gene was significantly associated with increased 2-year disease-free survival. The probability of surviving 2 years without tumor recurrence was 100% with promoter hypermethylation in 2 or 3 genes and 46% with promoter hypermethylation in none or just 1 gene (P=.013). Promoter hypermethylation of 2 or 3 genes was independently related to increased 2-year cumulative disease-free survival (P=.028). CONCLUSIONS: Promoter hypermethylation of hMLH1, MGMT, and p16 genes was commonly detected in 47 SCCHN cases with up to 65% showing aberrant promoter hypermethylation in at least 1 gene. Promoter hypermethylation of 2 or 3 genes was significantly associated with increased 2-year disease-free survival, suggesting that promoter hypermethylation of multiple genes might improve survival. Significant correlation was also noted between a positive alcohol use history and promoter hypermethylation of the MGMT gene with no promoter hypermethylation of the p16 gene.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Nuclear reprogramming of cloned embryos produced in vitro.

Despite the fact that cloned animals derived from somatic cells have been successfully generated in a variety of mammalian species, there are still many unsolved problems with current cloning technology. Somatic cell nuclear transfer has shown several developmental aberrancies, including a high rate of abortion during early gestation and increased perinatal death. One cause of these developmental failures of cloned embryos may reside in the epigenetic reprogramming of somatic donor genome. In mammals, DNA methylation is an essential process in the regulation of transcription during embryonic development and is generally associated with gene silencing. A genome-wide demethylation may be a prerequisite for the formation of pluripotent stem cells that are important for later development. We analyzed methylation patterns in cloned bovine embryos to monitor the epigenetic reprogramming process of donor genomic DNA. Aberrant methylation profiles of cloned bovine embryos were observed in various genomic regions, except in single-copy gene sequences. The overall genomic methylation status of cloned embryos was quite different from that of normal embryos produced in vitro or in vivo. These results suggest that the developmental failures of cloned embryos may be due to incomplete epigenetic reprogramming of donor genomic DNA. We expect that advances in understanding the molecular events for reprogramming of donor genome will contribute to clarify the developmental defects of cloned embryos.

Animals↗

PubMed2025

BMDx2: A Tool for Integrating Toxicogenomics-Based Dose-Dependency Analysis and AOP-Based Mechanistic Insights.

Despite the advent of mechanistic toxicology using omics data to link molecular perturbations with systemic outcomes, regulatory toxicology still lacks the application of mechanism-anchored metrics from such data. This is partially because traditional gene-centric analysis often falls short of linking molecular changes to adverse outcomes. To address this gap, BMDx2, an open-source tool that transforms multi-dose toxicogenomics datasets into quantitative, mechanistic evidence for human chemical safety assessment is developed. BMDx2 couples benchmark-dose modeling with Adverse Outcome Pathway (AOP) enrichment to derive transcriptomic-based points of departure, enabling potency ranking, chemical prioritization, and mechanistically anchored explanations of the effect of chemical exposures. BMDx2 can process a broad range of data, including DNA microarray and RNA sequencing studies. Here, case studies are used to illustrate the versatility of BMDx2 in characterizing the mechanism of action of chemicals. An initial case study on carbon nanotubes exposure applies integrative analysis of transcriptomics and genome-wide DNA methylation data, uncovering cellular reprogramming processes underlying fibrosis. A second case study on bleomycin exposure demonstrate how transcriptomic data alone can be mapped to fibrosis-related AOPs in a standardized, regulatory appropriate manner. Together, these examples show how BMDx2 supports the regulatory application of toxicogenomics and accelerates mechanism-based chemical safety evaluation.

Toxicogenetics↗

PubMed2025

Discovery of a DNA methylation episignature as a molecular biomarker for fetal alcohol syndrome.

PURPOSE: Fetal alcohol spectrum disorder (FASD) encompasses a range of clinical features and neurodevelopmental disorders in children exposed to alcohol in utero. Despite its global public health significance, FASD diagnosis remains challenging because of nonspecific clinical findings and the lack of an accurate molecular diagnostic biomarker. This study aimed to evaluate peripheral blood DNA methylation (DNAm) profiles as a potential diagnostic biomarker for fetal alcohol syndrome. METHODS: Genomic DNAm profiles from 93 individuals with suspected or confirmed FAS, including a clinically diagnosed FAS subgroup, were analyzed and compared with a large database of control and patient cohorts with previously reported DNAm episignatures. Functional analysis of these DNAm profiles was performed to identify episignatures and assess their potential diagnostic utility. RESULTS: A relatively sensitive and specific DNAm episignature for FAS was identified. Comparative epigenomic analysis revealed functional correlations between FAS and other rare genetic disorders, supporting the robustness of the identified DNAm profiles as a diagnostic tool. CONCLUSION: This study demonstrates that unique DNAm profiles provide a robust episignature biomarker for FAS. These findings contribute to the molecular understanding of FAS and hold promise for improving diagnostic accuracy for this complex disorder.

Humans↗

PubMedDate not supplied

Epigenetic silencing mediated by CpG island methylation: potential as a therapeutic target and as a biomarker.

Many genes become transcriptionally silenced during the development of cancer. As well as affecting disease progression, gene silencing has the potential to influence drug resistance and clinical outcome following therapy. In addition to silencing due to gene mutations, covalent epigenetic modifications such as DNA hypermethylation and histone post-translational modifications are associated with transcriptional inactivation of many genes and are an important early event during carcinogenesis and tumour development. Aberrant methylation of CpG islands in promoters is associated with transcriptional inactivation of genes involved in all aspects of tumour development. Genes involved in key DNA damage response pathways, such as cell cycle control, apoptosis signalling and DNA repair, can frequently become methylated and epigenetically silenced in tumours. This may lead to differences in intrinsic sensitivity of tumours to chemotherapy, depending on the specific function of the gene inactivated. Furthermore, it is proposed that chemotherapy itself can exert a selective pressure on epigenetically silenced drug sensitivity genes present in subpopulations of cells, leading to acquired chemoresistance. Since the DNA sequence of epigenetically inactivated genes are not mutated but rather subject to reversible modifications via DNA methyltransferases (DNMTs) or histone modification, it is possible to reverse silencing using small molecule inhibitors. Such compounds show anti-tumour activity and can increase the sensitivity of drug resistant preclinical tumour models. Clinical trials of epigenetic therapies are now underway. Epigenetic profiling, using DNA methylation and histone analysis, will provide guidance on optimisation of these therapies with conventional chemotherapy and will help identify patient populations who may particularly benefit from such approaches.

Animals↗

PubMed2026

Age and early life adversity shape heterogeneity of the epigenome across tissues in macaques.

Age and early life adversity (ELA) are key determinants of health, but whether they affect similar physiological mechanisms across tissues is unknown. We generated DNA methylation (DNAm) profiles across 14 tissues in 237 semi-free-ranging rhesus macaques with naturally occurring ELA. Age-associated DNAm was predominantly tissue dependent, yet tissue-specific epigenetic clocks showed that epigenetic aging was relatively consistent within individuals. ELA effects were adversity dependent, but each ELA exerted coordinated effects across tissues. Although ELA targeted many of the same loci as age, the directions of effects differed, which indicates that ELA does not uniformly increase epigenetic age. Instead, ELA leaves a coordinated, cross-tissue epigenetic signature that is distinct from-yet intertwined with-age-related differences, which advances our understanding of how early environments sculpt the molecular foundations of aging and disease.

Animals↗

PubMed2020

PTSD is associated with increased DNA methylation across regions of HLA-DPB1 and SPATC1L.

Posttraumatic stress disorder (PTSD) is characterized by intrusive thoughts, avoidance, negative alterations in cognitions and mood, and arousal symptoms that adversely affect mental and physical health. Recent evidence links changes in DNA methylation of CpG cites to PTSD. Since clusters of proximal CpGs share similar methylation signatures, identification of PTSD-associated differentially methylated regions (DMRs) may elucidate the pathways defining differential risk and resilience of PTSD. Here we aimed to identify epigenetic differences associated with PTSD. DNA methylation data profiled from blood samples using the MethylationEPIC BeadChip were used to perform a DMR analysis in 187 PTSD cases and 367 trauma-exposed controls from the Grady Trauma Project (GTP). DMRs were assessed with R package bumphunter. We identified two regions that associate with PTSD after multiple test correction. These regions were in the gene body of HLA-DPB1 and in the promoter of SPATC1L. The DMR in HLA-DPB1 was associated with PTSD in an independent cohort. Both DMRs included CpGs whose methylation associated with nearby sequence variation (meQTL) and that associated with expression of their respective genes (eQTM). This study supports an emerging literature linking PTSD risk to genetic and epigenetic variation in the HLA region.

Cytoskeletal Proteins↗

PubMed2026

Targeted long-read genomic and epigenomic profiling enhances timely comprehensive variant discovery in hypotonia and muscle weakness.

BACKGROUND: Identifying the genetic basis of hypotonia and muscle weakness is critical for patient management and family counseling. However, diagnosis is often hindered by diverse genomic alterations, including repeat expansions, structural variants (SVs), and methylation defects. Standard-of-care testing, largely based on short-read sequencing, is limited in its ability to detect this heterogeneous variation landscape, leaving many patients undiagnosed or requiring lengthy sequential testing. Long-read sequencing represents a promising solution. However, its application as a first-tier diagnostic assay for hypotonia remains unexplored. METHODS: We retrospectively analyzed 227 patients with hypotonia to assess diagnostic yield, time-to-diagnosis, and costs associated with standard-of-care testing. A long-read whole-genome sequencing (LR-WGS) workflow with targeted analysis of hypotonia-associated genes was developed to detect and prioritize pathogenic SNVs, SVs, and CNVs, repeat expansions, and methylation changes at key disease loci. The workflow was validated in a reference-positive cohort with known diagnoses (n = 15) and applied to an unsolved cohort (n = 14). Variant interpretation followed ACMG guidelines and was confirmed with orthogonal methods. RESULTS: Standard-of-care testing achieved a diagnostic yield of 42% with an average time-to-diagnosis of 68.7 days; however, 30% of diagnosed patients experienced significant delays (average 169 days) due to sequential testing. The LR-WGS based approach identified all known pathogenic variants in the positive cohort, including SMN1 deletions, methylation defects at 15q11.2/Prader-Willi locus, FMR1 repeat expansions, and sequence and copy-number variants in > 100 genes underlying myopathies and muscular dystrophies. The targeted long-read pipeline reduced prioritized variant calls by 97.9-99.9% and, in the unsolved cohort, yielded one definitive diagnosis (de novo COL6A3 deletion) and one possible diagnosis (aberrant methylation and copy number at POMK), for an additional 14% yield. Among patients diagnosed after sequential testing (n = 29), LR-WGS is expected to reduce time-to-diagnosis by ~ 85% and decrease cumulative diagnostic delays, with projected healthcare cost savings of $396,000-439,000. Across the entire 227 patient cohort, LR-WGS is anticipated to reduce testing costs by 6.5%, yielding an average savings of $105 per patient. CONCLUSIONS: LR-WGS enables comprehensive discovery of genomic and epigenomic variants in hypotonia and muscle weakness, improving diagnostic yield, shortening diagnostic timelines, and reducing costs compared with current standard-of-care testing.

Humans↗

PubMed2026

Exercise-associated epigenetic remodeling and TCR repertoire dynamics in Lynch syndrome carriers.

Lynch syndrome (LS) carriers are at elevated cancer risk. Emerging evidence suggests that exercise may serve as a non-pharmacologic preventive strategy, yet the epigenetic and immunological mechanisms underlying its protective effects in this population remain unclear. Here, we perform integrative multi-omics profiling of DNA methylation, gene expression, and the T cell receptor (TCR) repertoire in LS carriers undergoing a 52-week aerobic cycling intervention. We identify compartment-specific DNA methylation changes, including innate immune activation in cfDNA and oncogenic pathway repression in tissue. Integrative transcriptomic analysis highlights ISL1 as a key exercise-repressed, epigenetically regulated gene, and identifies FLCN as a colorectal cancer (CRC)-associated methylation target. TCR analysis reveals an exercise-associated increase in systemic repertoire diversity and tissue-specific clonal convergence, thus suggesting antigen-driven recruitment. Collectively, these findings uncover epigenetic and immune remodeling as potential mechanisms of exercise-mediated protection in LS.

Lynch syndrome↗

PubMed2006

Pharmacologic inhibition of epigenetic modifications, coupled with gene expression profiling, reveals novel targets of aberrant DNA methylation and histone deacetylation in lung cancer.

Lung cancer is the leading cause of cancer-related deaths in the United States due, in large part, to the lack of early detection methods. Lung cancer arises from a complex series of genetic and epigenetic changes leading to uncontrolled cell growth and metastasis. Unlike genetic changes, epigenetic changes, such as DNA methylation and histone acetylation, are reversible with currently available pharmaceuticals and are early events in lung tumorigenesis detectable by non-invasive methods. In order to better understand how epigenetic changes contribute to lung cancer, and to identify new disease biomarkers, we combined pharmacologic inhibition of DNA methylation and histone deacetylation in non-small cell lung cancer (NSCLC) cell lines, with genome-wide expression profiling. Of the more than 200 genes upregulated by these treatments, three of these, neuronatin, metallothionein 3 and cystatin E/M, were frequently hypermethylated and transcriptionally downregulated in NSCLC cell lines and tumors. Interestingly, four other genes, cylindromatosis, CD9, activating transcription factor 3 and oxytocin receptor, were dominantly regulated by histone deacetylation and were also frequently downregulated in lung tumors. The majority of these genes also suppressed NSCLC growth in culture when ectopically expressed. This study therefore reveals new putative NSCLC growth regulatory genes and epigenetic disease biomarkers that may enhance early detection strategies and serve as therapeutic targets.

Acetylation↗

PubMed2004

[Promoter methylation profile in breast cancer].

BACKGROUND: Genomic DNA methylation, mutations and allelic deletions explain the inactivation of genes involved in cell proliferation and cell cycle control mechanisms. AIM: To analyze the methylation pattern of important genes related to different carcinogenic mechanisms in patients with breast cancer and the relationship with its biological behavior. MATERIAL AND METHODS: Seventy fresh-frozen breast cancer samples were selected. The methylation specific PCR (MSP) test was used to analyze promoter methylation status for genes CDKN2A (p16), hMLH1, APC, CDH1 (Cadherin E) and FHIT. RESULTS: We found methylation in at least one of the genes studied in 88% of cases and in 3 or more genes in 40.5% of cases. The frequencies of promoter hypermethylation of CDKN2A, hMLH1, APC, CDH1 and FHT were 41.4%, 11.4%, 52.9%, 70% and 42.9%, respectively. We found a relationship between CDKN2A methylatlon and better survival (p=0.002). CDH1 methylation and poor histological differentiation (p=0.007), hMLH1 methylation and non-Mapuche ethnicity (p=-0.03), APC methylation and larger tumor size (p<0.05), FHIT methylatton and lack of estrogen rectptor IHC expression (p<0.05). CONCLUSIONS: The high frequency of promoter methylation in patients with breast cancer confirms its role in breast carcinogenesis. The finding of alterations in the methylation pattern of genes studied and its association with prognostic factors is a helpful tool in the search of new criteria for clinical and therapeutic decision making.

Acid Anhydride Hydrolases↗

PubMed2003

Epigenomic profiling using microarrays.

Genes occupy only a minor fraction of genomes such as ours; however, histone and nonhistone chromosomal proteins and methylated DNA bases are distributed over both genic and nongenic regions. These widespread "epigenomic" features can be mapped and characterized by alternative applications of the same microarray technologies that have been used for conventional transcriptional profiling. Here we describe diverse microarray-based strategies for profiling patterns of DNA methylation, DNA replication, DNA binding, and chromatin-associated proteins and histone modifications. The rapid progress that is being made in developing and applying epigenomic profiling methods and the increasing availability of microarrays mean that epigenomic profiling is likely to become a standard research tool for understanding chromatin structure and gene expression during development.

Animals↗

PubMed1986

Developmental and tissue-specific regulation of the Q10 class I gene by DNA methylation.

The H-2 class I genes encode cell-surface glycoproteins that play a critical role in the immune presentation of aberrant cells. The Q10 class I gene, however, encodes a secreted glycoprotein that is highly homologous to the membrane-bound molecules. While the H-2 genes are activated in all tissue types, the expression of the Q10 gene is restricted to only the liver. Analysis of DNA from different tissues revealed a unique methylation profile for the Q10 gene in liver. Developmental activation of this gene in newborn mice is also reflected by a coordinated temporal change in DNA methylation. By comparing the methylation profiles between congenic mice, which differed in their levels of expression of the Q10 gene, it is observed that methylation at the 3'-flanking region correlates with expression. Methylations were at both CG and CC sequences. Since treatment of newborns with 5-azacytidine, which led to inhibition of methylation, resulted in the suppression of Q10, we conclude that hypermethylation in the 3'-flanking region is responsible, at least in part if not in full, for the activation of the Q10 gene in the liver.

Animals↗

PubMed2026

DNA methylation landscape of cerebrospinal fluid cells in multiple sclerosis: an epigenome-wide association study.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system in which DNA methylation may link genetic and environmental risk factors. METHODS: We profiled genome-wide DNA methylation in cerebrospinal fluid (CSF) cells from people with MS (pwMS) and matched controls. Differentially methylated positions (DMPs) and regions (DMRs) were integrated with transcriptomic data, T-cell chromatin annotations, and pathway analyses. Protocadherin gamma (PCDHγ) expression was assessed in primary CD4+ T-cell subsets and confirmed by flow cytometry. FINDINGS: We identified 2710 DMPs and 4330 DMRs associating with genes that were enriched in immune signalling, adhesion and migration processes, and were accompanied by corresponding RNA changes. MS-associated methylation changes enriched in the cohesin chromatin-regulation pathway localised to T-cell regulatory regions, and this pathway included multiple protocadherin (PCDH) genes, which displayed consistent methylation and expression changes in CSF cells of pwMS compared to controls. PCDHγ cluster gene expression was detected in CD4+ T-cell subsets, and flow cytometry confirmed PCDHγ protein expression in peripheral blood T cells. Moreover, co-expression analysis suggests a role of PCDH genes in aryl hydrocarbon receptor (AHR) signalling. Protein-level validation showed fewer PCDHγ-positive CD4+ T cells in pwMS and activation-induced PCDHγ upregulation after T-cell stimulation. INTERPRETATION: DNA methylation changes in CSF resident cells reflect dysregulated T cell activation and migration in pwMS and suggest involvement of protocadherin molecules in MS pathogenesis. FUNDING: European Research Council, Swedish Research Council, Swedish Brain Foundation, Swedish MS Foundation, Knut and Alice Wallenberg Foundation, European Union and others.

Humans↗

PubMed2025

Cell-type-specific DNA methylation dynamics in the prenatal and postnatal human cortex.

The human cortex undergoes extensive epigenetic remodeling during development, although the precise temporal and cell-type-specific dynamics of DNA methylation remain incompletely understood. In this study, we profiled genome-wide DNA methylation across human cortex tissue from donors aged 6 post-conception weeks to 108 years of age. We observed widespread, developmentally regulated changes in DNA methylation, with pronounced shifts occurring during early- and mid-gestation that were distinct from age-associated modifications in the postnatal cortex. Using fluorescence-activated nuclei sorting, we optimized a protocol for the isolation of SATB2-positive neuronal nuclei, enabling the identification of cell-type-specific DNA methylation trajectories in the developing cortex. Developmentally dynamic DNA methylation sites were significantly enriched near genes implicated in autism and schizophrenia, supporting a role for epigenetic dysregulation in neurodevelopmental conditions. Our findings underscore the prenatal period as a critical window of epigenomic plasticity in the brain with important implications for understanding the genetic basis of neurodevelopmental phenotypes.

Humans↗

PubMed1995

Chromosomal insertion of foreign (adenovirus type 12, plasmid, or bacteriophage lambda) DNA is associated with enhanced methylation of cellular DNA segments.

Insertion of foreign DNA into an established mammalian genome can extensively alter the patterns of cellular DNA methylation. Adenovirus type 12 (Ad12)-transformed hamster cells, Ad12-induced hamster tumor cells, or hamster cells carrying integrated DNA of bacteriophage lambda were used as model systems. DNA methylation levels were examined by cleaving cellular DNA with Hpa II, Msp I, or Hha I, followed by Southern blot hybridization with 32P-labeled, randomly selected cellular DNA probes. For several, but not all, cellular DNA segments investigated, extensive increases in DNA methylation were found in comparison with the methylation patterns in BHK21 or primary Syrian hamster cells. In eight different Ad12-induced hamster tumors, moderate increases in DNA methylation were seen. Increased methylation of cellular genes was also documented in two hamster cell lines with integrated Ad12 DNA without the Ad12-transformed phenotype, in one cloned BHK21 cell line with integrated plasmid DNA, and in at least three cloned BHK21 cell lines with integrated lambda DNA. By fluorescent in situ hybridization, the cellular hybridization probes were located to different hamster chromosomes. The endogenous intracisternal A particle genomes showed a striking distribution on many hamster chromosomes, frequently on their short arms. When BHK21 hamster cells were abortively infected with Ad12, increases in cellular DNA methylation were not seen. Thus, Ad12 early gene products were not directly involved in increasing cellular DNA methylation. We attribute the alterations in cellular DNA methylation, at least in part, to the insertion of foreign DNA. Can alterations in the methylation profiles of hamster cellular DNA contribute to the generation of the oncogenic phenotype?

Adenoviridae↗

PubMed2006

Classification of DNA methylation patterns in tumor cell genomes using a CpG island microarray.

Our group has initiated experiments to epigenetically profile CpG island hypermethylation in genomic DNA from tissue specimens of head and neck squamous cell carcinoma (HNSCC) using a microarray of 12,288 CpG island clones. Our technique, known as a methylation-specific restriction enzyme (MSRE) analysis, is a variation of the differential methylation hybridization (DMH) technique, in that it is not an array comparison of two DNA samples using methylation-specific restriction enzymes. Instead, it is a comparison of a single DNA sample's response to a methylation-sensitive restriction enzyme (HpaII) and its corresponding methylation-insensitive isoschizomer (MspI). Estimation of the reproducibility of this microarray assay by intraclass correlation (ICC) demonstrated that in four replicate experiments for three tumor specimens, the ICC observed for a given tumor specimen ranged from 0.68 to 0.85 without filtering of data. Repeated assays achieved 87% concordance or greater for all tumors after filtering of array data by fluorescence intensity. We utilized hierarchical clustering on a population of 37 HNSCC samples to cluster tumor samples with similar DNA methylation profiles. Supervised learning techniques are now being utilized to allow us to identify associations between specific epigenetic signatures and clinical parameters. Such techniques will allow us to identify select groups of CpG island loci that could be used as epigenetic markers for both diagnosis and prognosis in HNSCC.

Blotting, Southern↗

PubMed2005

[Promoter methylation profile in gastric cancer].

BACKGROUND: Promoter genomic DNA methylation is an important inactivation mechanism of tumor suppressor genes. This genetic-molecular pathway for cancer may separate a subset of patients with different prognoses and eventually different responses to specific therapies. AIM: To analyze the methylation pattern of important genes related to different carcinogenic mechanisms in patients with gastric cancer (GC) and the relationship with its morphological features and biological behavior. MATERIAL AND METHODS: Forty-seven fresh-frozen GC samples were selected. The methylation-specific PCR (MSP) test was used to analyze promoter methylation status for genes MLH1, CDKN2A (p16), APC, CDH1 (Cadherin E) and FHIT. Follow-up and complete morphological features were obtained for all cases. RESULTS: We found methylation in at least one of the genes studied in 83% of the cases. The frequencies of promoter hypermethylation of MLH1, CDKN2A, APC, CDH1 and FHIT were 31%, 43%, 46%, 80% y 62%, respectively. We found a relationship between APC methylation and good histological differentiation (p =0.03); CDH1 methylation with diffuse type by Lauren and 3 or more metastasic lymph nodes (p <0.05); FHIT, CDKN2A and CDH1 methylation and female condition (p <0.04). We also found a non-significant relationship between CDKN2A methylation and better survival (p =0.07). CONCLUSIONS: The high frequency promoter methylation found confirms its importance in gastric carcinogenesis. The finding of alterations in the methylation pattern of genes studied and its association with prognostic factors is a helpful tool in the search for new criteria in clinical and therapeutic decision making.

Adult↗