scholarly journals Frequent DNA Hypermethylation at the RASSF1A and APC Gene Loci in Prostate Cancer Patients of Pakistani Origin

ISRN Urology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Ahmed Yaqinuddin ◽  
Sohail A. Qureshi ◽  
Shahid Pervez ◽  
Mohammed Umair Bashir ◽  
Ressam Nazir ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
Cancer Patients ◽  
Methylation Status ◽  
Transurethral Resection Of Prostate ◽  
Gene Promoters ◽  
Dna Hypermethylation ◽  
Pakistani Population ◽  
Specific Pcr ◽  
Pakistani Origin

DNA methylation has emerged as a potentially robust biomarker for prostate cancer (PCa). Since DNA methylomes appear to be disease as well as population specific, we have assessed the DNA methylation status of RASSF1A, APC, and p16 (potential biomarkers of PCa) in Pakistani population. Primary prostate cancer tissues were obtained from 27 formalin-fixed paraffin-embedded blocks (FFPE) of cancer patients who underwent radical prostatectomy and transurethral resection of prostate (TURP) during 2003–2008. As controls, twenty-four benign prostatic FFPE tissues were obtained from patients who underwent TURP for benign prostatic hyperplasia during 2008. DNA was extracted, and methylation-specific PCR was used to assess the methylation status for RASSF1A, APC, and p16 gene promoters. Our results revealed that the RASSF1A promoter was hypermethylated in all the tested cancer samples but was also hypermethylated in 3 out of 24 control tissues. The APC promoter was hypermethylated in 15 out of 27 cancer samples and in none of the control samples. Strikingly, none of the samples showed methylation at the p16 promoter. Our findings suggest that RASSF1A and APC gene promoters are frequently hypermethylated in the Pakistani population and therefore have the potential to develop into universally dependable biomarkers for detecting PCa.

UP-1.096: Frequent DNA Hypermethylation at the RASSF1A and APC Gene Loci in Prostate Cancer Patients of Pakistani Origin

Urology ◽  
2009 ◽  
Vol 74 (4) ◽  
pp. S199-S200
Author(s):  
A. Yaqinuddin ◽  
S. Qureshi ◽  
S. Pervez ◽  
M. Bashir ◽  
R. Nazir ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Apc Gene ◽  
Dna Hypermethylation ◽  
Pakistani Origin

scholarly journals Consistent DNA Hypermethylation Patterns in Laryngeal Papillomas

2010 ◽  
Vol 1 (2) ◽  
pp. 69-77 ◽  
Author(s):  
Josena K Stephen ◽  
Kang Mei Chen ◽  
Veena Shah ◽  
Vanessa G Schweitzer ◽  
Glendon Gardner ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Methylation Status ◽  
Promoter Hypermethylation ◽  
Aberrant Methylation ◽  
Dna Hypermethylation ◽  
Suppressor Genes ◽  
Multiple Tumor ◽  
Specific Pcr

Abstract 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 status was determined using the multigene (22 tumor suppressor genes) methylation-specific multiplex ligationdependent probe amplification assay and confirmed using methylation specific PCR. Results Twenty genes had altered DNA methylation in 22 of 25 cases. Aberrant methylation of CDKN2B and TIMP3 was most frequent. Promoter hypermethylation of BRCA2, APC, CDKN2A and CDKN2B was detected in 2 RRP cases with subsequent progression to SCC. Of the 25 cases, 22 were positive for HPV-6, 2 for HPV-11 and 1 for HPV-16 and 33. Conclusion Consistent aberrant methylation of multiple tumor suppressor genes contributes to the pathogenesis of laryngeal papillomas. Persistent aberrant DNA methylation events in 2 RRP cases that progressed to cancer indicate an epigenetic monoclonal progression continuum to SCC.

Abstract 40: Disturbed Flow Alters Genomewide DNA Methylation Patterns, Regulating Endothelial Gene Expression and Atherosclerosis

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Jessilyn Dunn ◽  
Haiwei Qiu ◽  
Soyeon Kim ◽  
Daudi Jjingo ◽  
Ryan Hoffman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Western Diet ◽  
Dependent Manner ◽  
Gene Promoters ◽  
Genome Wide ◽  
Methylation Patterns ◽  
Endothelial Gene Expression

Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow (d-flow), which alters gene expression, endothelial function, and atherosclerosis. Here, we show that d-flow regulates genome-wide DNA methylation patterns in a DNA methyltransferase (DNMT)-dependent manner. We found that d-flow induced expression of DNMT1, but not DNMT3a or DNMT3b, in mouse arterial endothelium in vivo and in cultured endothelial cells by oscillatory shear (OS) compared to unidirectional laminar shear in vitro. The DNMT inhibitor 5-Aza-2’deoxycytidine (5Aza) or DNMT1 siRNA significantly reduced OS-induced endothelial inflammation. Moreover, 5Aza reduced lesion formation in two atherosclerosis models using ApoE-/- mice (western diet for 3 months and the partial carotid ligation model with western diet for 3 weeks). To identify the 5Aza mechanisms, we conducted two genome-wide studies: reduced representation bisulfite sequencing (RRBS) and transcript microarray using endothelial-enriched gDNA and RNA, respectively, obtained from the partially-ligated left common carotid artery (LCA exposed to d-flow) and the right contralateral control (RCA exposed to s-flow) of mice treated with 5Aza or vehicle. D-flow induced DNA hypermethylation in 421 gene promoters, which was significantly prevented by 5Aza in 335 genes. Systems biological analyses using the RRBS and the transcriptome data revealed 11 mechanosensitive genes whose promoters were hypermethylated by d-flow but rescued by 5Aza treatment. Of those, five genes contain hypermethylated cAMP-response-elements in their promoters, including the transcription factors HoxA5 and Klf3. Their methylation status could serve as a mechanosensitive master switch in endothelial gene expression. Our results demonstrate that d-flow controls epigenomic DNA methylation patterns in a DNMT-dependent manner, which in turn alters endothelial gene expression and induces atherosclerosis.

scholarly journals Multiplexed DNA Methylation Analysis in Colorectal Cancer Using Liquid Biopsy and Its Diagnostic and Predictive Value

2021 ◽  
Vol 43 (3) ◽  
pp. 1419-1435
Author(s):  
Walter Pulverer ◽  
Kristi Kruusmaa ◽  
Silvia Schönthaler ◽  
Jasmin Huber ◽  
Marko Bitenc ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Therapy Monitoring ◽  
Methylation Status ◽  
Methylation Analysis ◽  
Microarray Experiments ◽  
Specific Pcr ◽  
Colonic Adenomas ◽  
Methylation Sensitive Restriction Enzyme ◽  
Dna Methylation Analysis

Early diagnosis of colorectal cancer (CRC) is of high importance as prognosis depends on tumour stage at the time of diagnosis. Detection of tumour-specific DNA methylation marks in cfDNA has several advantages over other approaches and has great potential for solving diagnostic needs. We report here the identification of DNA methylation biomarkers for CRC and give insights in our methylation-sensitive restriction enzyme coupled qPCR (MSRE-qPCR) system. Targeted microarrays were used to investigate the DNA methylation status of 360 cancer-associated genes. Validation was done by qPCR-based approaches. A focus was on investigating marker performance in cfDNA from 88 patients (44 CRC, 44 controls). Finally, the workflow was scaled-up to perform 180plex analysis on 110 cfDNA samples, to identify a DNA methylation signature for advanced colonic adenomas (AA). A DNA methylation signature (n = 44) was deduced from microarray experiments and confirmed by quantitative methylation-specific PCR (qMSP) and by MSRE-qPCR, providing for six genes’ single areas under the curve (AUC) values of >0.85 (WT1, PENK, SPARC, GDNF, TMEFF2, DCC). A subset of the signatures can be used for patient stratification and therapy monitoring for progressed CRC with liver metastasis using cfDNA. Furthermore, we identified a 35-plex classifier for the identification of AAs with an AUC of 0.80.

scholarly journals DNA Hypermethylation of a panel of genes as an urinary biomarker for bladder cancer diagnosis

2021 ◽  
Author(s):  
Petros Georgopoulos ◽  
Maria Papaioannou ◽  
Soultana Markopoulou ◽  
Aikaterini Fragou ◽  
George Kouvatseas ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bladder Cancer ◽  
Smoking Status ◽  
Gene Promoter ◽  
Control Group ◽  
Gene Promoters ◽  
Dna Hypermethylation ◽  
Diagnostic Potential ◽  
Specificity And Sensitivity ◽  
Promoter Dna

Abstract PurposeThe aim of this study was to explore the diagnostic potential of a panel of five hypermethylated gene promoters in bladder cancer. Individuals with primary BCa and control individuals matching the gender, age and smoking status of the cancer patients were recruited. DNA methylation was assessed for the gene promoters of RASSF1, RARβ, DAPK, hTERT and APC in urine samples collected by spontaneous urination. Fifty patients and 35 healthy controls were recruited, with average age of 70.26 years and average smoking status of 44.78 pack-years. In the BCa group, DNA methylation was detected in 27(61.4%) samples. RASSF1 was methylated in 52.2% of samples. Only 3(13.6%) samples from the control group were methylated, all in the RASSF1 gene promoter. The specificity and sensitivity of this panel of genes to diagnose BCa was 86% and 61% respectively. The RASSF1 gene could diagnose BCa with specificity 86.4% and sensitivity 52.3%. Promoter DNA methylation of this panel of five genes could be further investigated as urine biomarker for the diagnosis of BCa. The RASSF1 could be a single candidate biomarker for predicting BCa patients versus controls. Studies are required in order to develop a geographically adjusted diagnostic biomarker for BCa.Trial registration: ACTRN12620000258954

Search for Pharmacoepigenetic Correlations in Type 2 Diabetes Under Sulfonylurea Treatment

2018 ◽  
Vol 127 (04) ◽  
pp. 226-233 ◽  
Author(s):  
Makrina Karaglani ◽  
Georgia Ragia ◽  
Maria Panagopoulou ◽  
Ioanna Balgkouranidou ◽  
Evangelia Nena ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Promoter ◽  
Katp Channels ◽  
Protective Role ◽  
Gene Promoters ◽  
Specific Pcr ◽  
Abcc8 Gene ◽  
First Time ◽  
E23k Polymorphism

AbstractSulfonylureas are insulin secretagogues which act in pancreatic β cells by blocking the KATP channels encoded by KCNJ11 and ABCC8 genes. In the present study, a pharmacoepigenetic approach was applied for the first time, investigating the correlation of KCNJ11 and ABCC8 gene promoter methylation with sulfonylureas-induced mild hypoglycemic events as well as the KCNJ11 E23K genotype. Sodium bisulfite-treated genomic DNA of 171 sulfonylureas treated T2DM patients previously genotyped for KCNJ11 E23K, including 88 that had experienced drug-associated hypoglycemia and 83 that had never experienced hypoglycemia, were analyzed for DNA methylation of KCNJ11 and ABCC8 gene promoters via quantitative Methylation-Specific PCR. KCNJ11 methylation was detected in 19/88 (21.6%) of hypoglycemic and in 23/83 (27.7%) of non-hypoglycemic patients (p=0.353), while ABCC8 methylation in 6/83 (7.2%) of non-hypoglycemic and none (0/88) of the hypoglycemic patients (p=0.012). Methylation in at least one promoter (KCNJ11 or ABCC8) was significantly associated with non-hypoglycemic patients who are carriers of KCNJ11 EK allele (p=0.030). Our data suggest that ABCC8 but not KCNJ11 methylation is associated to hypoglycemic events in sulfonylureas-treated T2DM patients. Furthermore, it is demonstrated that the KCNJ11 E23K polymorphism in association to either of the two genes’ DNA methylation may have protective role against sulfonylurea-induced hypoglycemia.

scholarly journals Frequent DNA methylation changes in cancerous and noncancerous lung tissues from smokers with non-small cell lung cancer

Mutagenesis ◽  
2020 ◽  
Author(s):  
Kristina Daniunaite ◽  
Agne Sestokaite ◽  
Raimonda Kubiliute ◽  
Kristina Stuopelyte ◽  
Eeva Kettunen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Methylation Status ◽  
Small Cell ◽  
Study Cohort ◽  
Tumour Suppressor Genes ◽  
Epigenetic Changes ◽  
Small Cell Lung ◽  
Specific Pcr ◽  
Never Smokers

Abstract Cancer deaths account for nearly 10 million deaths worldwide each year, with lung cancer (LCa) as the leading cause of cancer-related death. Smoking is one of the major LCa risk factors, and tobacco-related carcinogens are potent mutagens and epi-mutagens. In the present study, we aimed to analyse smoking-related epigenetic changes in lung tissues from LCa cases. The study cohort consisted of paired LCa and noncancerous lung tissues (NLT) from 104 patients, 90 of whom were smokers or ex-smokers (i.e. ever smokers) at the time of diagnosis. DNA methylation status of tumour suppressor genes DAPK1, MGMT, p16, RASSF1 and RARB was screened by means of methylation-specific PCR (MSP) and further analysed quantitatively by pyrosequencing. Methylation of at least one gene was detected in 59% (61 of 104) of LCa samples and in 39% (41 of 104) of NLT. DAPK1 and RASSF1 were more frequently methylated in LCa than in NLT (P = 0.022 and P = 0.041, respectively). The levels of DNA methylation were higher in LCa than NLT at most of the analysed CpG positions. More frequent methylation of at least one gene was observed in LCa samples of ever smokers (63%, 57 of 90) as compared with never smokers (36%, 5 of 14; P = 0.019). In the ever smokers group, methylation of the genes also occurred in NLT, but was rare or absent in the samples of never smokers. Among the current smokers, RASSF1 methylation in LCa showed association with the number of cigarettes smoked per day (P = 0.017), whereas in NLT it was positively associated with the duration of smoking (P = 0.039). Similarly, p16 methylation in LCa of current smokers correlated with the larger number of cigarettes smoked per day (P = 0.047). Overall, DNA methylation changes were present in both cancerous and noncancerous tissues of LCa patients and showed associations with smoking-related parameters.

An integrative DNA methylation model for improved prognostication of postsurgery recurrence and therapy in prostate cancer patients

2020 ◽  
Vol 38 (2) ◽  
pp. 39.e1-39.e9 ◽  
Author(s):  
Renu Jeyapala ◽  
Shivani Kamdar ◽  
Ekaterina Olkhov-Mitsel ◽  
Andrea J Savio ◽  
Fang Zhao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
Cancer Patients
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