scholarly journals Association of Peripheral Blood RASSF1A and CDKN2A Methylation Status with Smoking Behaviour in Nasopharyngeal Carcinoma

2018 ◽  
Vol 10 (2) ◽  
pp. 123-7
Author(s):  
Erika Diana Risanti ◽  
Aditya Kurniawan ◽  
Laila Wahyuningsih ◽  
Ery Kus Dwianingsih ◽  
Hanggoro Tri Rinonce ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Nasopharyngeal Carcinoma ◽  
Peripheral Blood ◽  
Smoking Status ◽  
Methylation Status ◽  
Smoking Behavior ◽  
Promoter Hypermethylation ◽  
Smoking Behaviour ◽  
Chi Square ◽  
Aberrant Dna Methylation

BACKGROUND: Hypermethylation of RASSF1A and CDKN2A is one of epigenetic factor underlies nasopharyngeal carcinoma (NPC) development. Smoking behavior as an NPC’s risk factor causes aberrant DNA methylation. RASSF1A and CDKN2A promoter hypermethylation from peripheral blood cells correlates with smoking behavior. The use of body fluids including peripheral blood as a specimen for DNA methylation analyzes are widely developed, as less invasive method compared to the use of tissue biopsy. This study aims to observe the association between RASSF1A and CDKN2A methylation in peripheral blood and smoking behavioramong NPC patients.METHODS: Newly diagnosed NPC subjects were recruited from ear-nose-throat (ENT) outpatient clinic of Dr. Sardjito Hospital, Yogyakarta. DNA from buffycoat of 19 smokers and 20 non-smokers NPC’s patients were isolated. Bisulphite modification was applied to 500 ng of the isolated DNA. The methylation status was detected by MSP (methylation-specific polymerase chain reaction (PCR)). The association between smoking status and promoter hypermethylation was analysis using Chi-Square test.RESULTS: MSP analysis of RASSF1A showed that 68.42% smoker and 75% non-smoker NPC’s patients were methylated. MSP analysis of CDKN2A showed that 21.05% smoker and 25% non-smoker NPC’s patients were methylated. There was no association between smoking behavior with RASSF1A and CDKN2A methylation (p>0.05).CONCLUSION: Statistical analysis showed that smoking behavior is not associated with methylation of RASSF1A and CDKN2A among NPC’s patients.KEYWORDS: DNA methylation, CDKN2A, RASSF1A, Nasopharyngeal carcinoma, Smoking

scholarly journals DNA Methylation of Regulatory Regions of Imprinted Genes at Birth and Its Relation to Infant Temperament

2016 ◽  
Vol 8 ◽  
pp. GEG.S40538 ◽  
Author(s):  
Bernard F. Fuemmeler ◽  
Chien-Ti Lee ◽  
Adelheid Soubry ◽  
Edwin S. Iversen ◽  
Zhiqing Huang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Smoking Status ◽  
Small Sample Size ◽  
Methylation Status ◽  
Small Sample ◽  
Infant Temperament ◽  
Imprinted Genes ◽  
Blood Leukocytes ◽  
Regulatory Regions ◽  
Size Limits

BACKGROUND DNA methylation of the differentially methylated regions (DMRs) of imprinted genes is relevant to neurodevelopment. METHODS DNA methylation status of the DMRs of nine imprinted genes in umbilical cord blood leukocytes was analyzed in relation to infant behaviors and temperament (n = 158). RESULTS MEG3 DMR levels were positively associated with internalizing ( β = 0.15, P = 0.044) and surgency ( β = 0.19, P = 0.018) behaviors, after adjusting for birth weight, gender, gestational age at birth, maternal age at delivery, race/ethnicity, education level, smoking status, parity, and a history of anxiety or depression. Higher methylation levels at the intergenic MEG3-IG methylation regions were associated with surgency ( β = 0.28, P = 0.0003) and PEG3 was positively related to externalizing ( β = 0.20, P = 0.01) and negative affectivity ( β = 0.18, P = 0.02). CONCLUSION While the small sample size limits inference, these pilot data support gene-specific associations between epigenetic differences in regulatory regions of imprinted domains at birth and later infant temperament.

PPARγ preservation via promoter demethylation alleviates osteoarthritis in mice

2019 ◽  
Vol 78 (10) ◽  
pp. 1420-1429 ◽  
Author(s):  
Xiaobo Zhu ◽  
Fang Chen ◽  
Ke Lu ◽  
Ai Wei ◽  
Qing Jiang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Knockout Mice ◽  
Cartilage Damage ◽  
Critical Role ◽  
Methylation Status ◽  
Promoter Hypermethylation ◽  
Dna Methyltransferases ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Peroxisome Proliferator

ObjectivesOsteoarthritis (OA) is the most common degenerative joint disease in aged population and its development is significantly influenced by aberrant epigenetic modifications of numerous OA susceptible genes; however, the precise mechanisms that DNA methylation alterations affect OA pathogenesis remain undefined. This study investigates the critical role of epigenetic PPARγ (peroxisome proliferator–activated receptor-gamma) suppression in OA development.MethodsArticular cartilage expressions of PPARγ and bioactive DNA methyltransferases (DNMTs) from OA patients and mice incurred by DMM (destabilisation of medial meniscus) were examined. DNA methylation status of both human and mouse PPARγ promoters were assessed by methylated specific PCR and/or bisulfite-sequencing PCR. OA protections by a pharmacological DNA demethylating agent 5Aza (5-Aza-2'-deoxycytidine) were compared between wild type and PPARγ knockout mice.ResultsArticular cartilages from both OA patients and DMM mice display substantial PPARγ suppressions likely due to aberrant elevations of DNMT1 and DNMT3a and consequential PPARγ promoter hypermethylation. 5Aza known to inhibit both DNMT1 and DNMT3a reversed the PPARγ promoter hypermethylation, recovered the PPARγ loss and effectively attenuated the cartilage damage in OA mice. 5Aza also inhibited the OA-associated excessive inflammatory cytokines and deficit anti-oxidant enzymes, which were blocked by a specific PPARγ inhibitor in cultured chondrocytes. Further, 5Aza-confered protections against the cartilage damage and the associated abnormalities of OA-susceptible factors were significantly abrogated in PPARγ knockout mice.ConclusionEpigenetic PPARγ suppression plays a key role in OA development and PPARγ preservation via promoter demethylation possesses promising therapeutic potentials in clinical treatment of OA and the related joint diseases.

Genome-Wide Identification of Aberrant Promoter Associated CpG Island Methylation in Acute Lymphoblastic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2127-2127
Author(s):  
Shao-qing Kuang ◽  
Weigang Tong ◽  
Hui Yang ◽  
Mathew K. Lee ◽  
Zhi-Hong Fang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
B Cell ◽  
Cell Lines ◽  
Cpg Island ◽  
Trichostatin A ◽  
Methylation Status ◽  
Leukemia Cell ◽  
Human Leukemia ◽  
Leukemia Cell Lines ◽  
Aberrant Dna Methylation

Abstract Aberrant DNA methylation is a common molecular feature of both pediatric and adult ALL. Specific methylation patterns predict for poor prognosis (Shen et al Blood 2004), and reactivation of epigenetically inactivated molecular pathways results in induction of leukemia cell death (Kuang et al. Oncogene 2007). Until now most studies of methylation in ALL have been based on arbitrary gene selection methods. To overcome this limitation and to study hundreds of promoter CpG islands simultaneously, we have developed a method that combines MCA (Methylated CpG Island Amplification) with either RDA (Representational Difference Analysis) or the Agilent Promoter Microarray platform. With these methods differentially methylated DNA treated with bisulfite is generated after mixing tester DNA (in our case DNA from de novo refractory Ph negative and MLL negative ALL patients) with driver DNA (normal B cell controls) and using specific restriction enzymes and several rounds of PCR. DNA fragments thus generated are either cloned (RDA) or labeled and spotted on the Agilent Array. Using this technology, that can potentially interrogate up to 17K promoters, we have identified 932 promoters targets of aberrant DNA methylation in poor risk ALL from patients that cannot be currently identified by standard molecular methods (Ph and MLL negative). The genes associated with these promoters are distributed through the human genome but an overrepresentation of methylated promoters located in chromosomes 3, 9, 11 and 19 was detected. Using molecular pathway clustering analysis, 404 of these genes are grouped together in 29 specific functional pathways. We have validated the methylation of 31 of these 923 genes by bisulfite pyrosequencing. Of these, 27 (87%) were confirmed to be hypermethylated in 23 human leukemia cell lines but not in normal controls (N=15). Methylation status analysis of these 27 genes allowed for the segregation of T cell versus B cell leukemia cell lines. Fifteen of these genes (GIPC2, RSPO1, MAGI1, CAST1, ADCY5, HSPA4L, OCLN, EFNA5, MSX2, GFPT2, GNA14, SALL1, MYO5B, ZNF382 and MN1) were also frequently hypermethylated in primary ALL samples. Expression analysis of 6 of these genes (GIPC2, MAGI1, ADCY5, HSPA4L, OCLN and GNA14) in leukemia cell lines further confirmed methylation associated gene silencing. Treatment of methylated/silenced cell lines with 5′-aza-2′-deoxycytidine and trichostatin A resulted in gene re-expression, further confirming the role of DNA methylation in their silencing. In summary, we have identified in excess of 900 targets of aberrant DNA methylation in ALL. The study of the epigenetically suppressed pathways represented by these genes should allow us to further understand the molecular pathogenesis of ALL and develop new prognostic biomarkers for patients with Ph and MLL negative disease.

Azacytidine as a Maintenance Therapy in Elderly AML Progressively Demethylates CpG Sites within the p16 Gene

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4466-4466
Author(s):  
Margaret Dellett ◽  
Michelle Lazenby ◽  
Alan K Burnett ◽  
Ken I Mills
Keyword(s):  
Dna Methylation ◽  
Maintenance Therapy ◽  
Peripheral Blood ◽  
Age Of Onset ◽  
Methylation Status ◽  
Global Methylation ◽  
Cpg Sites ◽  
Number Of Patients ◽  
Elderly Aml ◽  
Diagnostic Samples

Abstract Acute myeloid leukemia (AML) accounts for ~30% of adult leukaemia cases and is expected to increase as the population ages, due to median age of onset at ~60 years old. Recent evidence suggests that DNA methylation is actively involved in AML and myelodysplastic syndrome (MDS). Tumor suppressor genes, such as p16, have been shown to be silenced by methylation in AML. However, epigenetic events such as DNA methylation are reversible and therefore targets for chemotherapeutic intervention. It has been reported that ~30% of MDS patients with an abnormal karyotype show normalization of their methylation status after receiving a demethylating drug during early stages of their therapy. The UK NCRI AML16 programme for elderly patients (>60 years old at diagnosis) with AML and high risk MDS has several therapeutic questions for patients considered fit for intensive treatment, one of which is to compare the use of azacytidine demethylation maintenance treatment with no maintenance therapy. Samples were obtained from patients entered into the AML16 trial, at diagnosis and from patients entered into the intensive arm of the trial who were randomized to receive azacytidine maintenance therapy were analyzed for the alterations for genomic methylation. Pyrosequencing was used to determine methylation within 17 CpG sites within p16, MLH1, and MGMT whilst LINE1 was used as a measure of global methylation. To date, approximately 714 patients have been entered into AML16. Of these 195 diagnostic samples have been analyzed, of which 103 were in the intensive arm of the trial. At the second randomization stage, 34 patient samples were analyzed and a further 26 samples were obtained following 3, 6 or 9 courses of azacytidine therapy. Statistical comparison of the methylation levels at each individual CpG or for the averaged CpG in each gene studies indicated that there was no difference whether the sample was derived from bone marrow or peripheral blood. This allowed the direct comparison of peripheral blood samples obtained at 2nd randomization and during azacytidine maintenance courses. Differential levels of methylation at individual CpG within the gene were seen at diagnosis. Higher levels of average p16 methylation were observed in the AML patients when compared to a small cohort of “well elderly” individuals. No difference was noted in the individual or averaged CpG methylation status for MGMT or LINE1 during the maintenance course of azacytidine. However, the methylation status of the CpG sites within the p16 and MLH1 genes reduced during maintenance by a median of 19% and 25% respectively. However, the number of patients completing three courses of azacytidine was only about 20% of those entering the intensive arm of AML16, however sequential samples from the same individual also showed demethylation of the CpG sites in p16 and MLH1. This study shows that azacytidine maintenance therapy in elderly AML patients does reduce the methylation status of some genes whilst others genes show no response. This is being investigated further using arrays containing 12,000 CpG sites which will be correlated with gene expression microarrays on the diagnostic samples from AML16.

scholarly journals Early Pregnancy Peripheral Blood DNA Methylation and Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study

2021 ◽  
Author(s):  
Xiaolei Wang ◽  
Jin Huang ◽  
Sisi Long ◽  
Huijun Lin ◽  
Na Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Dna Methylation ◽  
Peripheral Blood ◽  
Case Control Study ◽  
Methylation Status ◽  
First Trimester ◽  
Case Control ◽  
Cpg Sites ◽  
Nested Case Control ◽  
Control Study

Abstract Introduction: Genome-wide DNA methylation profiling has been used to identify CpG sites relevant to gestational diabetes mellitus (GDM). However, these sites have not been verified in larger samples. Here, our aim was to evaluate the changes in target CpG sites in the peripheral blood of pregnant women with GDM in their first trimester. Research Design and Methods: This nested case-control study examined a large cohort of women with GDM in early pregnancy (10–15 weeks; n = 80). Target CpG sites were extracted from related published literature and bioinformatics analysis. The DNA methylation levels at 337 CpG sites located in 27 target genes were determined using MethylTarget™ sequencing. The best cut-off levels for methylation of CpG sites were determined using the generated ROC curve. The independent effect of CpG site methylation status on GDM was analyzed using conditional logistic regression. Results Methylation levels at 6 CpG sites were significantly higher in the GDM group than in controls, whereas those at 7 CpG sites were significantly lower (P < 0.05). The area under the ROC curve at each methylation level of the significant CpG sites ranged between 0.593 and 0.650 for GDM prediction. After adjusting for possible confounders, the hypermethylation status of candidate sites cg68167324 (OR = 3.168, 1.038–9.666) and cg24837915 (OR = 5.232, 1.659–16.506) was identified as more strongly associated with GDM; conversely, the hypermethylation of sites cg157130156 (OR = 0.361, 0.135–0.966) and cg89438648 (OR = 0.206, 0.065–0.655) might indicate lower risk of GDM. Conclusions The methylation status of target CpG sites in the peripheral blood of pregnant women during the first trimester is associated with GDM pathogenesis, and has potential as a predictor of GDM.

scholarly journals HUBUNGAN ANTARA PERILAKU MEROKOK DENGAN KEJADIAN PENYAKIT JANTUNG KORONER

e-CliniC ◽  
2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Ratnawulan Afriyanti ◽  
Janry Pangemanan ◽  
Stella Palar
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Smoking Habit ◽  
Smoking Behavior ◽  
Smoking Behaviour ◽  
Chi Square ◽  
Cross Sectional ◽  
Consecutive Sampling ◽  
Number Of Patients ◽  
Disease Case

Abstract: Coronary Heart Disease is an ilness wich has high mortality rate either in developed or in developing country. In the entire world, a number of patients who suffer this desease still increases each year. Cigarette, is widely acclaimed to be the cause of death in the world. Thus, the smoking habit is very dangerous to the health. A bad habit has a power in damaging a person’s health, as smoking habit which can cause a person susceptible to get cardiovascular disease. Smoking is a major risk factor to get a heart disease which has strong correlation to the case of coronary heart disease. Smoking behaviour assessed based on the duration of smoking, the types of smoker, and the kind of cigarette. This research used the analytic descriptive study with a cross-sectional approach. The people being samples in this research are patients who suffer coronary heart disease in Polyclinic Center of Heart- Blood Vessel and Brain Unity of RSUP Prof. Dr. R. D. Kandou Manado. The research conducted during October – December 2014. In this research, the researcher used consecutive sampling as the technique in taking samples. The data got in this research were analyzed by using Chi-Square statistical test. The result of Chi-Square experiment showed that there is a significant correlation between smoking behavior and coronary heart disease case based on the duration of smoking (p= 0,010), the type of smoker (p=0,014) and the kind of cigarette to be smoked (p=0,001). Conclusion: There is a significant correlation between the duration of smoking, the types of smoker, and the kind of cigarette to be smoked with the case of coronary heart disease.Keywords: smoking behavior, coronary heart disease.Abstrak: Penyakit Jantung Koroner (PJK) adalah penyakit dengan angka mortalitas yang tinggi baik di negara maju maupun negara berkembang. Diseluruh dunia, jumlah pasien penyakit ini terus bertambah dari tahun ke tahun. Rokok secara luas telah menjadi salah satu penyebab kematian di dunia dan kebiasaan merokok merupakan perilaku yang berbahaya bagi kesehatan. Kebiasaan dan rutinitas yang merugikan memiliki kekuatan untuk merusak kesehatan seseorang seperti kebiasaan merokok yang merupakan contoh kebiasaan untuk memudahkan seseorang terkena penyakit kardiovaskuler. Merokok merupakan faktor risiko mayor untuk terjadinya penyakit jantung, dan memiliki hubungan kuat untuk terjadinya PJK. Penelitian ini bertujuan untuk mengetahui hubungan antara perilaku merokok dengan kejadian penyakit jantung koroner. Perilaku merokok dinilai berdasarkan lama merokok, tipe perokok, dan jenis rokok. Penelitian ini menggunakan studi deskriptif analitik dengan pendekatan potong lintang/cross-sectional. Sampel dalam penelitian ini adalah pasien Penyakit Jantung Koroner di Poli Klinik Pusat Jantung – Pembuluh Darah dan Otak Terpadu RSUP Prof. Dr. R. D. Kandou Manado periode Oktober 2014 – Desember 2014 dengan teknik pengambilan sampel consecutive sampling. Data dianalisa dengan menggunakan uji statistik Chi-Square. Hasil uji Chi-square menunjukkan bahwa terdapat hubungan yang signifikan antara perilaku merokok dan kejadian penyakit jantung koroner berdasarkan lama merokok (P = 0,010 ), tipe perokok (P = 0,014) dan jenis rokok yang dihisap (P = 0,001). Simpulan: Terdapat hubungan yang signifikan antara lama merokok, tipe perokok dan jenis rokok yang dihisap dengan kejadian penyakit jantung koroner.Kata kunci: perilaku merokok, penyakit jantung koroner

scholarly journals DNA Methylation Status of SHOX-Flanking CpG Islands in Healthy Individuals and Short Stature Patients with Pseudoautosomal Copy Number Variations

2019 ◽  
Vol 158 (2) ◽  
pp. 56-62 ◽  
Author(s):  
Kenichiro Ogushi ◽  
Atsushi Hattori ◽  
Erina Suzuki ◽  
Hirohito Shima ◽  
Masako Izawa ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Short Stature ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Copy Number ◽  
Methylation Status ◽  
Cpg Islands ◽  
Copy Number Variations ◽  
Peripheral Blood Cells ◽  
Healthy Individuals

SHOX resides in the short arm pseudoautosomal region (PAR1) of the sex chromosomes and escapes X inactivation. SHOX haploinsufficiency underlies idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis (LWD). A substantial percentage of cases with SHOX haploinsufficiency arise from pseudoautosomal copy number variations (CNVs) involving putative enhancer regions of SHOX. Our previous study using peripheral blood samples showed that some CpG dinucleotides adjacent to SHOX exon 1 were hypomethylated in a healthy woman and methylated in a woman with gross X chromosomal rearrangements. However, it remains unknown whether submicroscopic pseudoautosomal CNVs cause aberrant DNA methylation of SHOX-flanking CpG islands. In this study, we examined the DNA methylation status of SHOX-flanking CpG islands in 50 healthy individuals and 10 ISS/LWD patients with pseudoautosomal CNVs. In silico analysis detected 3 CpG islands within the 20-kb region from the translation start site of SHOX. Pyrosequencing and bisulfite sequencing of genomic DNA samples revealed that these CpG islands were barely methylated in peripheral blood cells and cultured chondrocytes of healthy individuals, as well as in peripheral blood cells of ISS/LWD patients with pseudoautosomal CNVs. These results, in conjunction with our previous findings, indicate that the DNA methylation status of SHOX-flanking CpG islands can be affected by gross X-chromosomal abnormalities, but not by submicroscopic CNVs in PAR1. Such CNVs likely disturb SHOX expression through DNA methylation-independent mechanisms, which need to be determined in future studies.

High Frequency of Tumor Suppressor Genes Promoter Hypermethylation in Peripheral Blood of Patients with Myelodysplastic Syndromes

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4468-4468
Author(s):  
Patrizia Bossolasco ◽  
Francesco Onida ◽  
Giorgia Saporiti ◽  
Carla Bozzi ◽  
Clara Ricci ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
High Frequency ◽  
Mononuclear Cells ◽  
Methylation Status ◽  
Promoter Hypermethylation ◽  
Differential Rate ◽  
Cell Cycle Regulator

Abstract Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell disorders characterized by ineffective hematopoiesis and peripheral blood cytopenias, with very little established about their pathogenesis. DNA methylation is a common modification thought to be relevant to carcinogenesis. The epigenetic silencing, through methylation of CpG islands within the promoter regions, is one of the mechanisms by which numerous genes are inactivated in MDS and acute myeloid leukemias (AML). In particular, the promoter of CDKN2B (encoding p15INK4b), has been shown to be hypermethylated in poor-risk subtypes of MDS and often predicts transformation to AML. In this study, we examined the promoter methylation status of 7 genes in peripheral blood (PB) cells collected from 19 patients affected by untreated MDS. We investigated genes involved in cell cycle regulation (p14ARF, p15INK4b, p16INK4a), apoptosis (SPARC, DAPK1), differentiation (RARb) and response to growth factors (RASSF1A) previously reported as being abnormally hypermethylated in acute leukemia and in a variety of solid malignancies. DNA was extracted from PB low-density mononuclear cells and promoters methylation status was analyzed by means of methylation-specific PCR assay (MSP). MSP distinguishes unmethylated from methylated alleles in a given gene based on sequence changes produced after bisulfite treatment of DNA, which converts unmethylated (but not methylated) cytosines to uracil, and subsequent PCR using primers designed for either methylated or unmethylated DNA. Sodium bisulfite modification was performed using the Methylamp DNA Modification Kit (Epigentek) following manufacturer‘s instructions. Our series included 4 RA, 3 RARS, 3 RCMD, 2 RCMD/RS, 5 RAEB-1, 1 RAEB-2 and 1 CMML-1; according to the IPSS, 17 patients (89%) were classified as either low- or intermediate-1 risk. Median age was 72 years (range 49–86). Cytogenetics were normal in 12 patients (63%), while in 3 patients showed the 5q- abnormality. Median CBC counts were: WBC 3.1 × 109/L (0.9–12.5), Hb 10 g/dl (6.4–15), PLT 106 × 109/L (9–406). The cell cycle regulator p15INK4b was found to be the most frequently hypermethylated gene (14/19 pts, 74%) in our MDS series, followed by the p14ARF (13/19 pts, 68%). The latter was hypermethylated in 100% of our 5q- cases. Ninety-five percent (18/19 pts) of the MDS samples were found to be hypermethylated in at least one of the seven genes, with the only exception being the patient with CMML (unmethylated in all the tested genes). Hypermethylation of the cell cycle regulator p16INK4a was detected in 47% of samples. In 3 patients (16%) we found hypermethylation in all genes but RASSF1A, which indeed was found unmethylated in all but one of the samples analyzed (5%). The tumor suppressor gene SPARC was hypermethylated in 58% of patients (including 2 out of the 3 cases of 5q-), whereas 42% and 47% of samples, respectively, showed hypermethylation of the RARb and DAPK1 genes promoter. Although in a limited number of samples, we detected a differential rate of hypermethylation of the tested genes in peripheral blood of MDS patients. Altogether, our results seem to confirm high frequency of hypermethylation genes involved in regulation of cell cycle and apoptosis in MDS. We conclude that mononuclear cells from peripheral blood represents an easily accessible sample for detection and monitoring of genes promoter hypermethylation in myelodysplastic syndromes.

Aberrant DNA Methylation in Childhood Acute Lymphoblastic Leukemia as a Potential Biomarker Reflecting Disease Status.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2637-2637
Author(s):  
Seung Yeon Kwon ◽  
Sung Chul Won ◽  
Hyo Sun Kim ◽  
Hei-Cheul Jeung ◽  
Sun Young Rha ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Complete Resolution ◽  
Poor Prognosis ◽  
Lymphoblastic Leukemia ◽  
Methylation Status ◽  
Disease Status ◽  
Childhood All ◽  
Remission Status ◽  
Potential Biomarker ◽  
Aberrant Dna Methylation

Abstract Abstract 2637 Poster Board II-613 Background: Aberrant DNA methylation of promoter-associated cystosine-guanine (CpG) islands is known to play an important role in leukemogenesis and has been reported to have association with poor prognosis in acute lymphoblastic leukemia (ALL). In adult, residual methylation at clinical remission status in patients with acute myeloid leukemia and Philadelphia chromosome-positive ALL showed significant association with poor prognosis in recent studies. We analyzed 47 patients with childhood ALL to evaluate the change of methylation status from the time of diagnosis to the time at morphologic remission. Methods: We analyzed the methylation status of CDH1, p16 and DAPK genes at the time of diagnosis and at the time of morphologic remission in 47 patients using methylation specific polymerase chain reaction method with genomic DNA extracted from bone marrow (BM) aspirates. All patients were treated with standard chemotherapy and after 4 weeks, every patient achieved morphologic complete remission. Methylation status of above three genes were also analyzed with the same method in 10 BM aspirate samples from healthy BM donor for comparison. Results: CDH1 was methylated in 30 (64%) patients, p16 in 2 (4%) patients and DAPK in 6 (13%) patients at the time of diagnosis. Thirty three (70%) patients had methylation at least one gene, and 5 (11%) had methylation of 2 genes. None of the healthy BM donors showed methylation of above genes. At the time of morphologic remission, all patients who had aberrant DNA methylation of any gene at the time of diagnosis had no detectable residual methylation showing complete resolution of aberrant DNA methylation of examined genes. Clinical prognostic factors including initial white blood cell count, immunophenotype and presence of specific translocations (TEL-AML1, BCR-ABL, E2A-PBX1) did not show any association with initial methylation status. Age was the only factor which showed correlation with methylation status; patients under 2 year old showed significantly low frequency of methylation of above three genes (p <0.001). Conclusion: Since aberrant DNA methylation of CDH1, p16 and DAPK genes were found in 70% of pretreatment ALL patients and none in healthy BM donor showing complete resolution of methylation at morphologic remission status, we cautiously suggest aberrant DNA methylation as a potential biomarker reflecting disease status in childhood ALL. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document