Realgar (α-As4S4) Treats Myelodysplastic Syndromes through Reducing DNA Hypermethylation / 中国结合医学杂志

DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes (MDS). Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes, inducing gene silencing. Realgar (α-As4S4) is a traditional medicine used for the treatment of various diseases in the ancient time. Realgar was reported to have efficacy for acute promyelocytic leukemia (APL). It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS. This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS, as well as the species and metabolisms of arsenic in vivo.

Chinese Medicine Regulates DNA Methylation to Treat Haematological Malignancies: A New Paradigm of "State-Target Medicine" / 中国结合医学杂志

Aberrant regulation of DNA methylation plays a crucial causative role in haematological malignancies (HMs). Targeted therapy, aiming for DNA methylation, is an effective mainstay of modern medicine; however, many issues remain to be addressed. The progress of epigenetic studies and the proposed theory of "state-target medicine" have provided conditions to form a new treatment paradigm that combines the "body state adjustment" of CM with targeted therapy. We discussed the correlation between Chinese medicine (CM) syndromes/states and DNA methylation in this paper. Additionally, the latest research findings on the intervention and regulation of DNA methylation in HMs, including the core targets, therapy status, CM compounds and active components of the Chinese materia medica were concisely summarized to establish a theoretical foundation of "state-target synchronous conditioning" pattern of integrative medicine for HMs, simultaneously leading a new perspective in clinical diagnosis and therapy.

DNA Methylation and Transcription of HLA-F and Serum Cytokines Relate to Chinese Medicine Syndrome Classification in Patients with Chronic Hepatitis B / 中国结合医学杂志

OBJECTIVE@#To explore the molecular bases of Chinese medicine (CM) syndrome classification in chronic hepatitis B (CHB) patients in terms of DNA methylation, transcription and cytokines.@*METHODS@#Genome-wide DNA methylation and 48 serum cytokines were detected in CHB patients (DNA methylation: 15 cases; serum cytokines: 62 cases) with different CM syndromes, including dampness and heat of Gan (Liver) and gallbladder (CHB1, DNA methylation: 5 cases, serum cytokines: 15 cases), Gan stagnation and Pi (Spleen) deficiency (CHB2, DNA methylation: 5 cases, serum cytokines: 15 cases), Gan and Shen (Kidney) yin deficiency (CHB3, DNA methylation: 5 cases, serum cytokines: 16 cases), CHB with hidden symptoms (HS, serum cytokines:16 cases) and healthy controls (DNA methylation: 6 cases). DNA methylation of a critical gene was further validated and its mRNA expression was detected on enlarged samples. Genome-wide DNA methylation was detected using Human Methylation 450K Assay and furthered verified using pyrosequencing. Cytokines and mRNA expression of gene were evaluated using multiplex biometric enzyme-linked immunosorbent assay (ELISA)-based immunoassay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively.@*RESULTS@#Totally 28,667 loci, covering 18,403 genes were differently methylated among CHB1, CHB2 and CHB3 (P<0.05 and |Δβ value| > 0.17). Further validation showed that compared with HS, the hg19 CHR6: 29691140 and its closely surrounded 2 CpG loci were demethylated and its mRNA expressions were significantly up-regulated in CHB1 (P<0.05). However, they remained unaltered in CHB2 (P>0.05). Levels of Interleukin (IL)-12 were higher in CHB3 and HS than that in CHB1 and CHB2 groups (P<0.05). Levels of macrophage inflammatory protein (MIP)-1α and MIP-1β were higher in CHB3 than other groups and leukemia inhibitory factor level was higher in CHB1 and HS than CHB2 and CHB3 groups (P<0.05). IL-12, MIP-1α and MIP-1β concentrations were positively correlated with human leukocyte antigen F (HLA-F) mRNA expression (R2=0.238, P<0.05; R2=0.224, P<0.05; R=0.447, P<0.01; respectively). Furthermore, combination of HLA-F mRNA and differential cytokines greatly improved the differentiating accuracy among CHB1, CHB2 and HS.@*CONCLUSIONS@#Demethylation of CpG loci in 5' UTR of HLA-F may up-regulate its mRNA expression and HLA-F expression was associated with IL-12, MIP-1α and MIP-1β levels, indicating that HLA-F and the differential cytokines might jointly involve in the classification of CM syndromes in CHB.@*REGISTRATION NO@#ChiCTR-RCS-13004001.

Epigenetic clocks in the pediatric population: when and why they tick? / 中华医学杂志(英文版)

Recent research efforts have provided compelling evidence of genome-wide DNA methylation alterations in pediatrics. It is currently well established that epigenetic clocks, composed of DNA methylation sites, can estimate the gestational and chronological age of cells and tissues from different ages. Also, extensive research is aimed at their correlation with early life exposure and pediatric diseases. This review aimed to systematically summarize the epigenetic clocks in the pediatric population. Publications were collected from PubMed and Web of Science databases up to Apr 2021. Epigenetic clocks, DNA methylation clocks, epigenetic age acceleration or deceleration, pediatric and the pediatric population were used as search criteria. Here, we first review the currently applicative pediatric epigenetic clocks. We then highlight the interpretation for epigenetic age deviations in the pediatric population and their association with external factors, developmental trajectories, and pediatric diseases. Considering the remaining unknown of pediatric clocks, research strategies into them are also discussed. In all, pediatric epigenetic clocks may act as potent tools to understand development, growth and diseases in early life.

Genome-wide DNA methylation patterns in monocytes derived from patients with primary Sjogren syndrome / 中华医学杂志(英文版)

BACKGROUND@#Epigenetics, especially DNA methylation, plays an important role in the pathogenesis of primary Sjogren syndrome (pSS). Our study aimed to reveal the role of DNA methylation in peripheral monocytes of pSS patients.@*METHODS@#A total of 11 pSS patients and five age-matched healthy controls (HCs) were included in this study. Monocytes were isolated from peripheral blood mononuclear cells using magnetic microbeads. DNA methylation profiles were generated using Human Methylation 850K BeadChips.@*RESULTS@#In monocytes from pSS patients, we identified 2819 differentially methylated positions (DMPs), comprising 1977 hypomethylated- and 842 hypermethylated-DMPs, corresponding to 1313 unique genes when compared with HCs. IFI44L, MX1, PAARP9, and IFITM1, which influence the interferon (IFN) signaling pathway, were among the genes hypomethylated in pSS. Functional analysis of genes with a minimum of two DMPs showed involvement in antigen binding, transcriptional regulation, cell adhesion, IFN-γ pathway, type I IFN pathway, antigen presentation, Epstein-Barr virus infection, human T-lymphotropic virus type 1 virus infection, and metabolic disease-related pathways. In addition, patients with higher serum IgG levels exhibited enrichment in Notch signaling and metabolic-related pathways. Upon comparing monocytes with salivary gland epithelial cells, an important overlap was observed in the cell cycle, cell senescence, and interleukin-17 signaling pathways. The differentially methylated genes were more enriched in the ribosome- and AMP-activated protein kinase signaling pathway in anti-Ro/SSA and anti-La/SSB autoantibodies double-positive patients.@*CONCLUSION@#Genome-wide DNA methylation profiling revealed significant differences in DNA methylation in monocytes isolated from patients with pSS.

miR-9-1 gene methylation and DNMT3B (rs2424913) polymorphism may contribute to periodontitis

Abstract Genetic and epigenetic changes have been associated with periodontitis in various genes; however, little is known about genes involved in epigenetic mechanisms and in oxidative stress. Objective: This study aims to investigate the association of polymorphisms C677T in MTHFR (rs1801133) and −149C→T in DNMT3B (rs2424913), as well as the methylation profiles of MTHFR, miR-9-1, miR-9-3, SOD1, and CAT with periodontitis. The association between polymorphisms and DNA methylation profiles was also analyzed. Methodology: The population studied was composed of 100 nonsmokers of both sexes, divided into healthy and periodontitis groups. Genomic DNA was extracted from the epithelial buccal cells, which were collected through a mouthwash. Polymorphism analysis was performed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while methylation-specific PCR (MSP) or combined bisulfite restriction analysis techniques were applied for methylation analysis. Results: For DNMT3B, the T allele and the TT genotype were detected more frequently in the periodontitis group, as well as the methylated profile on the miR-9-1 promoter region. There was also a tendency towards promoter region methylation on the CAT sequence of individuals with periodontal disease. Conclusion: The polymorphism −149C→T in DNMT3B (rs2424913) and the methylated profile of the miR-9-1 promoter region are associated with periodontitis.

Epigenetics in non-small cell lung carcinomas / Epigenetica en carcinomas pulmonares de células no pequeñas

Abstract: Objective: To perform a systematic review of the main epigenetic aberrations involved in non-small cell lung carcinomas' (NSCLC) diagnosis, progression, and therapeutics. Materials and methods: We performed a systematic review of the scientific literature on lung cancer epigenetics, focusing on NSCLC. Results: Several advances in the molecular study of classical epigenetic mechanisms and massive studies of lung cancer epigenome have contributed relevant new evidence revealing that various molecular complexes are functionally influencing genetic-epigenetic and transcriptional mechanisms that promote lung tumorigenesis (initiation, promotion, and progression), and are also involved in NSCLC therapy-resistance mechanisms. Conclusion: Several epigenetic complexes and mechanisms must be analyzed and considered for the design of new and efficient therapies, which could be fundamental to develop an integrated knowledge to achieve a comprehensive lung cancer personalized medicine.

Resumen: Objetivo: Realizar una revisión sistemática y estructurada de las principales aberraciones epigenéticas involucradas en el diagnóstico, progresión y terapia del cáncer pulmonar de células no pequeñas (CPCNP). Material y métodos: Revisión sistemática de literatura científica sobre epigenética del cáncer pulmonar del grupo CPCNP. Resultados: El estudio de los diversos mecanismos epigenéticos y su impronta epigenética en el epigenoma del cáncer pulmonar han arrojado nuevas evidencias a nivel biológico, biomédico y médico-clínico del impacto que los mecanismos epigenético-transcripcionales promueven de manera activa y reversible sobre los procesos de tumorigénesis, progresión histopatológica y mecanismos de resistencia a la terapia oncológica pulmonar. Conclusión: Deben analizarse diferentes complejos y mecanismos epigenéticos para el estudio y diseño de esquemas nuevos y eficaces de terapia epigenética, los cuales podrían ser fundamentales para desarrollar un conocimiento integral en el desarrollo de la medicina personalizada en el cáncer pulmonar del grupo CPCNP.

Methylation status of the PPP1R13L promoter region among lung cancer patients and healthy controls. Analytical cross-sectional study

ABSTRACT BACKGROUND: There is evidence that genetic predisposition and epigenetic alteration (e.g. DNA methylation) play major roles in lung cancer. In our genetic epidemiological studies, rs1970764 in oncogene PPP1R13L was most consistently associated with lung cancer risk. Here, we explored the role of PPP1R13L methylation in lung cancer development. DESIGN AND SETTING: Analytical cross-sectional study (45 lung cancer cases and 45 controls), conducted in China. METHODS: We investigated the DNA methylation status of 2,160 cytosine-phosphate-guanine (CpG) sites in the PPP1R13L promoter region using the EpiTYPER assay of the Sequenom MassARRAY platform. RESULTS: In the whole study group, the methylation levels of CpG-6, CpG-9, CpG-20 and CpG-21 were significantly lower and those of CpG-16 were significantly higher in cases than in controls. Among smokers, the methylation levels at five CpG sites (CpG-6, CpG-11, CpG-15, CpG-20 and CpG-21) were statistically significantly lower among cases. Among men, the methylation levels at four CpG sites (CpG-11, CpG-15, CpG-20 and CpG-21) were significantly lower among cases. Regarding smokers, the methylation levels at CpG-7.8 and CpG-21 among cases and at CpG-22 among controls were significantly lower, compared with nonsmokers. The frequency of positivity for methylation was not significantly different between lung cancer cases and controls (68.22% for cases and 71.87% for controls; P = 0.119). CONCLUSION: Our study on a Chinese population suggests that lung cancer patients have aberrant methylation status (hypomethylation tended to be more frequent) in peripheral blood leukocytes at several CpG sites in the PPP1R13L promoter region and that exposure to smoking may influence methylation status.

Effects of DACT1 methylation status on invasion and metastasis of nasopharyngeal carcinoma

BACKGROUND: The purpose of the present study was to investigate the role of the methylation status of the DACT1 gene on the invasion and metastasis of nasopharyngeal carcinoma cells. METHODS: The levels of methylation and expression of the DACT1 gene in nasopharyngeal carcinoma tissues and CNE2 cells were determined by methylation-specific PCR and RT-PCR, respectively. CNE2 cells were treated with 5-aza-2-deoxycytidine, and the variation in the methylation status of the DACT1 gene was detected, as well as the influence of methylation on invasiveness of nasopharyngeal carcinoma cells. RESULTS: The DACT1 gene was hyper-methylated in 44 of 62 cases of nasopharyngeal carcinoma. The DACT1 gene was hyper-methylated in 32 of 38 cases of nasopharyngeal carcinoma with lymph node metastasis, and the DACT1 gene was hyper-methylated in 7 of 24 cases of nasopharyngeal carcinoma without lymph node metastasis. The DACT1 mRNA level was weakly expressed or not expressed in all nasopharyngeal carcinoma tissues with hyper-methylated DACT1 genes; however, the DACT1 mRNA level was highly expressed in nasopharyngeal carcinoma tissues with low expression of the methylated DACT1 gene. The DACT1 gene was hyper-methylated and not expressed in CNE2 cells that did not have 5-aza-2-deoxycytidine treatment. After 5-aza-2-deoxycytidine treatment, the DACT1 gene was demethylated and the expression of DACT1 was restored. Moreover, the invasion ability was inhibited in CNE2 cells treated with 5-aza-2-deoxycytidine. CONCLUSION: The expression of DACT1 was related to the methylation status. High expression of DACT1 may inhibit the invasion and metastasis of nasopharyngeal carcinoma cells.

Alterações na epigenética do sistema ocitocinérgico em resposta ao cuidado materno negligente / Epigenetics changes into the oxytocinergic system in response to negligent maternal care

O cuidado materno negligente, a falta de afeto e a dificuldade de interagir socialmente estão relacionadas com o desequilíbrio neurofisiológico da ocitocina, neurormônio com papel importante de modulação dos comportamentos sociais. Em seres humanos existem ligações conhecidas entre o estresse pré-natal e perinatal e transtornos psiquiátricos e de desenvolvimento. O objetivo deste estudo foi revisar o conceito de epigenética com foco no efeito a longo prazo do cuidado materno negligente e sua relação com alterações do sistema ocitocinérgico baseado em estudos com animais e humanos. Uma revisão narrativa da literatura foi realizada entre junho de 2017 e janeiro de 2019 através da busca de estudos na base PUBMED, com foco nos resultados qualitativos das relações epigenéticas com a negligência infantil, doenças psiquiátricas e sistema ocitocinérgico. Os estudos referidos demonstram que o cuidado materno negligente é um fator de risco para o desenvolvimento de transtornos mentais, principalmente os que incluem sintomas de desordem social. A ocitocina, por agir como uma potente mediadora das interações sociais, confiança e controle da ansiedade, parece ter papel fundamental neste contexto. A notória transgeracionalidade dos transtornos encontrados em proles de mães negligentes parece estar envolvida com mecanismos epigenéticos que inativam genes específicos do sistema ocitocinérgico no sistema nervoso central. (AU)

Negligent maternal care, lack of affection and difficulty in social interaction are related to a neurophysiological imbalance in oxytocin levels, an important modulator of social behaviors. In humans there are known links between prenatal and perinatal stress and psychiatric and developmental disorders. This study aimed to review the concept of epigenetics with a focus on the long-term effect of negligent maternal care and its relationship to changes in the oxytocinergic system, based on animal and human studies. A narrative review of the literature was conducted using studies from June 2017 to January 2019 available in the PUBMED database, focusing on qualitative results of epigenetic relationships with child neglect, psychiatric diseases and oxytocinergic system. These studies demonstrate that negligent maternal care is a risk factor for the development of mental disorders, especially those that include symptoms of social disorder. Oxytocin, as a neurohormone that acts as a potent mediator of social interactions, confidence and anxiety control, seems to play a fundamental role in this context. The notorious transgenerationality of the disorders found in the offspring of negligent mothers seems to be due to epigenetic mechanisms that inactivate specific genes of the oxytocinergic system in the central nervous system.

Insights on the epigenetic mechanisms underlying pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH), characterized by localized increased arterial blood pressure in the lungs, is a slow developing long-term disease that can be fatal. PAH is characterized by inflammation, vascular tone imbalance, pathological pulmonary vascular remodeling, and right-sided heart failure. Current treatments for PAH are palliative and development of new therapies is necessary. Recent and relevant studies have demonstrated that epigenetic processes may exert key influences on the pathogenesis of PAH and may be promising therapeutic targets in the prevention and/or cure of this condition. The aim of the present mini-review is to summarize the occurrence of epigenetic-based mechanisms in the context of PAH physiopathology, focusing on the roles of DNA methylation, histone post-translational modifications and non-coding RNAs. We also discuss the potential of epigenetic-based therapies for PAH.

Global and gene-specific DNA methylation and hydroxymethylation in human skin exposed and not exposed to sun radiation

Abstract: Background: epigenomes can be influenced by environmental factors leading to the development of diseases. Objective: To investigate the influence of sun exposure on global DNA methylation and hydroxymethylation status and at specific sites of the miR-9-1, miR-9-3 and MTHFR genes in skin samples of subjects with no history of skin diseases. Methods: Skin samples were obtained by punch on sun-exposed and sun-protected arm areas from 24 corpses of 16-89 years of age. Genomic DNA was extracted from skin samples that were ranked according to Fitzpatrick's criteria as light, moderate, and dark brown. Global DNA methylation and hydroxymethylation and DNA methylation analyses at specific sites were performed using ELISA and MSP, respectively. Results: No significant differences in global DNA methylation and hydroxymethylation levels were found among the skin areas, skin types, or age. However, gender-related differences were detected, where women showed higher methylation levels. Global DNA methylation levels were higher than hydroxymethylation levels, and the levels of these DNA modifications correlated in skin tissue. For specific sites, no differences among the areas were detected. Additional analyses showed no differences in the methylation status when age, gender, and skin type were considered; however, the methylation status of the miR-9-1 gene seems to be gender related. Study limitations: there was no separation of dermis and epidermis and low sample size. Conclusion: sun exposure does not induce changes in the DNA methylation and hydroxymethylation status or in miR-9-1, miR-9-3 and MTHFR genes for the studied skin types.

Epigenética del síndrome de ovario poliquístico / Epigenetics of polycystic ovary syndrome

Polycystic ovarian syndrome (PCOS) is an endocrine and metabolic dysfunction, highly prevalent in women in their reproductive years. Hyperandrogenism, oligo-ovulation, polycystic ovarian morphology are the main features of this syndrome. PCOS is a genetic disorder with a multifactorial etiology and has a strong link with environmental components. It is frequently associated with obesity and insulin resistance. Recently, epigenetic mechanisms have been involved in the pathogenesis of PCOS. Several studies showed that methylation in DNA and miRNAs is altered in women with PCOS in blood, serum, adipose tissue, granulose cells and theca. This evidence indicates that women with PCOS have a different epigenetic regulation, which might be triggered by an adverse intrauterine environment or by postnatal environmental elements such as diet and or obesity.

Caracterización de pacientes con cáncer colorrectal esporádico basado en la nueva subclasificación molecular de consenso / Characterization of patients with sporadic colorectal cancer following the new Consensus Molecular Subtypes (CMS)

Background: Colorectal cancer (CRC) is an heterogeneous disease. Three carcinogenic pathways determine its molecular profile: microsatellite instability (MSI), chromosomal instability (CIN) and CpG island methylator phenotype (CIMP). Based on the new molecular classification, four consensus CRC molecular subtypes (CMS) are established, which are related to clinical, pathological and biological characteristics of the tumor. Aim: To classify Chilean patients with sporadic CRC according to the new consensus molecular subtypes of carcinogenic pathways. Material and Methods: Prospective analytical study of 53 patients with a mean age of 70 years (55% males) with CRC, operated at a private clinic, without neoadjuvant treatment. From normal and tumor tissue DNA of each patient, CIN, MSI and CIMP were analyzed. Combining these variables, tumors were classified as CMS1/MSI-immune, CMS2/canonical, CMS3/metabolic and CMS4/mesenchymal. Results: CMS1 tumors (19%) were located in the right colon, were in early stages, had MMR complex deficiencies and 67% had an activating mutation of the BRAF oncogene. CMS2 tumors (31%) were located in the left colon, had moderate differentiation, absence of vascular invasion, lymphatic and mucin. CMS3 tumors (29%) were also left-sided, with absence of vascular and lymphatic invasion, and 29% had an activating mutation of the KRAS oncogene. CMS4 tumors (21%) showed advanced stages and presence of metastases. Conclusions: This new molecular classification contributes to understanding the heterogeneity of tumors. It is possible to differentiate molecular subgroups of a single pathological diagnosis of adenocarcinoma, opening the door to personalized medicine.

Research Progress on the Detection Method of DNA Methylation and Its Application in Forensic Science / 法医学杂志

As an important part of epigenetic marker, DNA methylation involves in the gene regulation and attracts a wide spread attention in biological auxology, geratology and oncology fields. In forensic science, because of the relative stable, heritable, abundant, and age-related characteristics, DNA methylation is considered to be a useful complement to the classic genetic markers for age-prediction, tissue-identification, and monozygotic twins' discrimination. Various methods for DNA methylation detection have been validated based on methylation sensitive restriction endonuclease, bisulfite modification and methylation-CpG binding protein. In recent years, it is reported that the third generation sequencing method can be used to detect DNA methylation. This paper aims to make a review on the detection method of DNA methylation and its applications in forensic science.

DNA demethylation during Chrysanthemum floral transition following short-day treatment

Background: Analytical techniques such as methylation-sensitive amplification polymorphism and high-performance liquid chromatography were used to detect variation in DNA methylation of mature Chrysanthemum leaves during the floral transition induced by short-day (SD) treatment. Results: For both early- and late-flowering cultivars, the time from the date of planting to the appearance of the capitulum bud and early blooming were significantly shorter than those of the control. The capitulum development of the early-flowering cultivar was significantly accelerated compared to the control, unlike the late-flowering cultivar. The DNA methylation percentage of leaves was significantly altered during flower development. For the early-flowering cultivar, DNA methylation was 42.2-51.3% before the capitulum bud appeared and 30.5-44.5% after. The respective DNA methylation percentages for the late-flowering cultivar were 43.5-56% and 37.2-44.9%. Conclusions: The DNA methylation percentage of Chrysanthemum leaves decreased significantly during floral development. The decline in DNA methylation was elevated in the early-flowering cultivar compared with the late-flowering cultivar.

La metilación global del ADN y los niveles de homocisteína en plasma se encuentran disminuidos en pacientes con diabetes mellitus tipo 1 / Global DNA methylation and homocysteine levels are lower in type 1 diabetes patients

Background: The worldwide rise in the incidence of Type 1 Diabetes (T1D), and the concordance rate between monozygotic twins (50%), indicate a strong effect of the environment as an underlying factor of this disease. This process can occur throughout epigenetic modifications of gene expression such as DNA methylation, in which several nutrients participate as cofactors. Aim: To determine DNA methylation status in T1D patients and if it is related to plasma levels of folates and homocysteine (Hcy). Material and Methods: We obtained blood samples from 25 T1D patients aged 13.7 ± 5.9 years (11 males) and 25 healthy subjects aged 31.1 ± 7.8 years (16 males). DNA methylation was measured using a colorimetric kit in extracted DNA. Results are expressed as median (interquartile range). Results: Compared with healthy controls, T1D patients had lower global DNA methylation (0.85 (0.91) % and 1.25 (1.16) % respectively, p < 0.02) and Hcy levels (4.8 (1.1) µmol/L and 7.3 (1.4) µmol/L respectively p < 0.01). There were no differences in folate levels between groups. A significant association between folates and global DNA methylation status was observed in T1D patients (r = -0.564, p < 0.01) and healthy subjects (r = 0.440, p = 0.03). Conclusions: TD1 patients had lower levels of Hcy and global DNA methylation. It is relevant to further investigate if this imbalance also induces epigenetic changes in a gene-specific manner, especially in key genes involved in T1D pathogenesis.

Colorectal cancer DNA methylation patterns from patients in Manaus, Brazil

BACKGROUND: DNA methylation is commonly linked with the silencing of the gene expression for many tumor suppressor genes. As such, determining DNA methylation patterns should aid, in times to come, in the diagnosis and personal treatment for various types of cancers. Here, we analyzed the methylation pattern from five colorectal cancer patients from the Amazon state in Brazil for four tumor suppressor genes, viz.: DAPK, CDH1, CDKN2A, and TIMP2 by employing a polymerase chain reaction (PCR) specific to methylation. Efforts in the study of colorectal cancer are fundamental as it is the third most of highest incidence in the world. RESULTS: Tumor biopsies were methylated in 1/5 (20 %), 2/5 (40 %), 4/5 (80 %), and 4/5 (80 %) for CDH1, CDKN2A, DAPK, and TIMP2 genes, respectively. The margin biopsies were methylated in 3/7 (43 %), 2/7 (28 %), 7/7 (100 %), and 6/7 (86 %) for CDH1, CDKN2A, DAPK, and TIMP2, respectively. CONCLUSIONS: Our findings showed DAPK and TIMP2 to be methylated in most samples from both tumor tissues and adjacent non-neoplastic margins; thus presenting distinct methylation patterns. This emphasizes the importance of better understanding of the relation of these patterns with cancer in the context of different populations.