scholarly journals DNA Methylation Array Analysis Identifies Profiles of Blood-Derived DNA Methylation Associated With Bladder Cancer

2011 ◽  
Vol 29 (9) ◽  
pp. 1133-1139 ◽  
Author(s):  
Carmen J. Marsit ◽  
Devin C. Koestler ◽  
Brock C. Christensen ◽  
Margaret R. Karagas ◽  
E. Andres Houseman ◽  
...  

Purpose Epigenetic alterations in tissues targeted for cancer play a causal role in carcinogenesis. Changes in DNA methylation in nontarget tissues, specifically peripheral blood, can also affect risk of malignant disease. We sought to identify specific profiles of DNA methylation in peripheral blood that are associated with bladder cancer risk and therefore serve as an epigenetic marker of disease susceptibility. Methods We performed genome-wide DNA methylation profiling on participants involved in a population-based incident case-control study of bladder cancer. Results In a training set of 112 cases and 118 controls, we identified a panel of 9 CpG loci whose profile of DNA methylation was significantly associated with bladder cancer in a masked, independent testing series of 111 cases and 119 controls (P < .0001). Membership in three of the most methylated classes was associated with a 5.2-fold increased risk of bladder cancer (95% CI, 2.8 to 9.7), and a model that included the methylation classification, participant age, sex, smoking status, and family history of bladder cancer was a significant predictor of bladder cancer (area under the curve, 0.76; 95% CI, 0.70 to 0.82). CpG loci associated with bladder cancer and aging had neighboring sequences enriched for transcription-factor binding sites related to immune modulation and forkhead family members. Conclusion These results indicate that profiles of epigenetic states in blood are associated with risk of bladder cancer and signal the potential utility of epigenetic profiles in peripheral blood as novel markers of susceptibility to this and other malignancies.

Oncotarget ◽  
2016 ◽  
Vol 7 (39) ◽  
pp. 64191-64202 ◽  
Author(s):  
Qiuqiong Tang ◽  
Tim Holland-Letz ◽  
Alla Slynko ◽  
Katarina Cuk ◽  
Frederik Marme ◽  
...  

2014 ◽  
Vol 136 (8) ◽  
pp. 1845-1855 ◽  
Author(s):  
Rongxi Yang ◽  
Katrin Pfütze ◽  
Manuela Zucknick ◽  
Christian Sutter ◽  
Barbara Wappenschmidt ◽  
...  

2019 ◽  
Vol 48 (D1) ◽  
pp. D890-D895 ◽  
Author(s):  
Zhuang Xiong ◽  
Mengwei Li ◽  
Fei Yang ◽  
Yingke Ma ◽  
Jian Sang ◽  
...  

Abstract Epigenome-Wide Association Study (EWAS) has become an effective strategy to explore epigenetic basis of complex traits. Over the past decade, a large amount of epigenetic data, especially those sourced from DNA methylation array, has been accumulated as the result of numerous EWAS projects. We present EWAS Data Hub (https://bigd.big.ac.cn/ewas/datahub), a resource for collecting and normalizing DNA methylation array data as well as archiving associated metadata. The current release of EWAS Data Hub integrates a comprehensive collection of DNA methylation array data from 75 344 samples and employs an effective normalization method to remove batch effects among different datasets. Accordingly, taking advantages of both massive high-quality DNA methylation data and standardized metadata, EWAS Data Hub provides reference DNA methylation profiles under different contexts, involving 81 tissues/cell types (that contain 25 brain parts and 25 blood cell types), six ancestry categories, and 67 diseases (including 39 cancers). In summary, EWAS Data Hub bears great promise to aid the retrieval and discovery of methylation-based biomarkers for phenotype characterization, clinical treatment and health care.


2021 ◽  
Author(s):  
Petros Georgopoulos ◽  
Maria Papaioannou ◽  
Soultana Markopoulou ◽  
Aikaterini Fragou ◽  
George Kouvatseas ◽  
...  

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


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii400-iii401
Author(s):  
Kuo-Sheng Wu ◽  
Tai-Tong Wong

Abstract BACKGROUND Medulloblastoma (MB) was classified to 4 molecular subgroups: WNT, SHH, group 3 (G3), and group 4 (G4) with the demographic and clinical differences. In 2017, The heterogeneity within MB was proposed, and 12 subtypes with distinct molecular and clinical characteristics. PATIENTS AND METHODS: PATIENTS AND METHODS We retrieved 52 MBs in children to perform RNA-Seq and DNA methylation array. Subtype cluster analysis performed by similarity network fusion (SNF) method. With clinical results and molecular profiles, the characteristics including age, gender, histological variants, tumor location, metastasis status, survival, cytogenetic and genetic aberrations among MB subtypes were identified. RESULTS In this cohort series, 52 childhood MBs were classified into 11 subtypes by SNF cluster analysis. WNT tumors shown no metastasis and 100% survival rate. All WNT tumors located on midline in 4th ventricle. Monosomy 6 presented in WNT α, but not in β subtype. SHH α and β occurred in children, while SHH γ in infant. Among SHH tumors, α subtype showed the worst outcome. G3 γ showed the highest metastatic rate and worst survival associated with MYC amplification. G4 α has the highest metastatic rate, however G4 γ showed the worst survival. CONCLUSION We identified molecular subgroups and subtypes of MBs based on gene expression and DNA methylation profile in children in our cohort series. The results may contribute to the establishment of nation-wide correlated optimal diagnosis and treatment strategies for MBs in infant and children.


Author(s):  
Marina Bibikova ◽  
Bret Barnes ◽  
Chan Tsan ◽  
Vincent Ho ◽  
Brandy Klotzle ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 859 ◽  
Author(s):  
Anouk E. Hentschel ◽  
Jakko A. Nieuwenhuijzen ◽  
Judith Bosschieter ◽  
Annina P. van Splunter ◽  
Birgit I. Lissenberg-Witte ◽  
...  

DNA methylation analysis of full void urine and urine pellet seems promising for bladder cancer (BC) detection and surveillance. Urinary cell-free DNA from urine supernatant is now gaining interest for other molecular tests in BC. This study aims to evaluate which urine fraction is preferred for BC diagnosis using methylation markers: full void urine, urine pellet or supernatant. Methylation levels of nine markers were determined in the three urine fractions and correlated with their respective tumor tissues in BC patients and compared to controls. For all markers and marker panel GHSR/MAL, diagnostic performance was determined by calculating the area under the curve (AUC) of the respective receiver operating characteristic curves. For most of the markers, there was a significant correlation between the methylation levels in each of the urine fractions and the matched tumor tissues. Urine pellet was the most representative fraction. Generally, AUCs for BC diagnosis were comparable among the fractions. The highest AUC was obtained for GHSR/MAL in urine pellet: AUC 0.87 (95% confidence interval: 0.73–1.00), corresponding to a sensitivity of 78.6% and a specificity of 91.7%. Our results demonstrate that cellular and cell-free DNA in urine can be used for BC diagnosis by urinary methylation analysis. Based on our comparative analysis and for practical reasons, we recommend the use of urine pellet.


Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
Author(s):  
Rebecca V. Zhang ◽  
Kathleen A. Ryan ◽  
Haley Lopez ◽  
Marcella A. Wozniak ◽  
Michael S. Phipps ◽  
...  

Background and Purpose: Approximately 8% of Blacks have sickle cell trait (SCT), and there are conflicting reports from recent cohort studies on the association of SCT with ischemic stroke (IS). Most prior studies focused on older populations, with few data available in young adults. Methods: A population-based case-control study of early-onset IS was conducted in the Baltimore-Washington region between 1992 and 2007. From this study, 342 Black IS cases, ages 15 to 49, and 333 controls without IS were used to examine the association between SCT and IS. Each participant’s SCT status was established by genotyping and imputation. For analysis, χ 2 tests and logistic regression models were performed with adjustment for potential confounding variables. Results: Participants with SCT (n=55) did not differ from those without SCT (n=620) in prevalence of hypertension, previous myocardial infarction, diabetes mellitus, and current smoking status. Stroke cases had increased prevalence in these risk factors compared with controls. We did not find an association between SCT and early-onset IS in our overall population (odds ratio=0.9 [95% CI, 0.5–1.7]) or stratified by sex in males (odds ratio=1.26 [95% CI, 0.56–2.80]) and females (odds ratio=0.67 [95% CI, 0.28–1.69]). Conclusions: Our data did not find evidence of increased risk of early-onset stroke with SCT.


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