scholarly journals Dysregulation of DNA Methylation and Epigenetic Clocks in Prostate Cancer among Puerto Rican Men

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 2
Author(s):  
Anders Berglund ◽  
Jaime Matta ◽  
Jarline Encarnación-Medina ◽  
Carmen Ortiz-Sanchéz ◽  
Julie Dutil ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
Stem Cell ◽  
The United States ◽  
Epigenetic Clock ◽  
Normal Tissues ◽  
Differentially Methylated Genes ◽  
Stem Cell Divisions ◽  
Methylation Patterns ◽  
Ancestry Proportions

In 2021, approximately 248,530 new prostate cancer (PCa) cases are estimated in the United States. Hispanic/Latinos (H/L) are the second largest racial/ethnic group in the US. The objective of this study was to assess DNA methylation patterns between aggressive and indolent PCa along with ancestry proportions in 49 H/L men from Puerto Rico (PR). Prostate tumors were classified as aggressive (n = 17) and indolent (n = 32) based on the Gleason score. Genomic DNA samples were extracted by macro-dissection. DNA methylation patterns were assessed using the Illumina EPIC DNA methylation platform. We used ADMIXTURE to estimate global ancestry proportions. We identified 892 differentially methylated genes in prostate tumor tissues as compared with normal tissues. Based on an epigenetic clock model, we observed that the total number of stem cell divisions (TNSC) and stem cell division rate (SCDR) were significantly higher in tumor than adjacent normal tissues. Regarding PCa aggressiveness, 141 differentially methylated genes were identified. Ancestry proportions of PR men were estimated as African, European, and Indigenous American; these were 24.1%, 64.2%, and 11.7%, respectively. The identification of DNA methylation profiles associated with risk and aggressiveness of PCa in PR H/L men will shed light on potential mechanisms contributing to PCa disparities in PR population.

scholarly journals Differential DNA Methylation in Prostate Tumors from Puerto Rican Men

2021 ◽  
Vol 22 (2) ◽  
pp. 733
Author(s):  
Gilberto Ruiz-Deya ◽  
Jaime Matta ◽  
Jarline Encarnación-Medina ◽  
Carmen Ortiz-Sanchéz ◽  
Julie Dutil ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Repair ◽  
The United States ◽  
Dna Repair Genes ◽  
Prostate Tumors ◽  
The Us ◽  
Hispanic Latinos ◽  
Methylation Patterns ◽  
Ancestry Proportions ◽  
Repair Genes

In 2020, approximately 191,930 new prostate cancer (PCa) cases are estimated in the United States (US). Hispanic/Latinos (H/L) are the second largest racial/ethnic group in the US. This study aims to assess methylation patterns between aggressive and indolent PCa including DNA repair genes along with ancestry proportions. Prostate tumors classified as aggressive (n = 11) and indolent (n = 13) on the basis of the Gleason score were collected. Tumor and adjacent normal tissue were annotated on H&E (Haemotoxylin and Eosin) slides and extracted by macro-dissection. Methylation patterns were assessed using the Illumina 850K DNA methylation platform. Raw data were processed using the Bioconductor package. Global ancestry proportions were estimated using ADMIXTURE (k = 3). One hundred eight genes including AOX1 were differentially methylated in tumor samples. Regarding the PCa aggressiveness, six hypermethylated genes (RREB1, FAM71F2, JMJD1C, COL5A3, RAE1, and GABRQ) and 11 hypomethylated genes (COL9A2, FAM179A, SLC17A2, PDE10A, PLEKHS1, TNNI2, OR51A4, RNF169, SPNS2, ADAMTSL5, and CYP4F12) were identified. Two significant differentially methylated DNA repair genes, JMJD1C and RNF169, were found. Ancestry proportion results for African, European, and Indigenous American were 24.1%, 64.2%, and 11.7%, respectively. The identification of DNA methylation patterns related to PCa in H/L men along with specific patterns related to aggressiveness and DNA repair constitutes a pivotal effort for the understanding of PCa in this population.

scholarly journals Recruitment of NCOR1 to VDR target genes is enhanced in prostate cancer cells and associates with altered DNA methylation patterns

2012 ◽  
Vol 34 (2) ◽  
pp. 248-256 ◽  
Author(s):  
C. L. Doig ◽  
P. K. Singh ◽  
V. K. Dhiman ◽  
J. L. Thorne ◽  
S. Battaglia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
Cancer Cells ◽  
Target Genes ◽  
Prostate Cancer Cells ◽  
Methylation Patterns

scholarly journals Atlas of Age- and Tissue-specific DNA Methylation during Early Development of Barley (Hordeum vulgare)

2018 ◽  
Author(s):  
Moumouni Konate ◽  
Michael J. Wilkinson ◽  
Banjamin Mayne ◽  
Eileen Scott ◽  
Bettina Berger ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Hordeum Vulgare ◽  
Organ Function ◽  
Tissue Specific ◽  
Organ Differentiation ◽  
Differentiated Cells ◽  
Differentially Methylated Genes ◽  
Organ Specific ◽  
Development And Differentiation ◽  
Methylation Patterns

The barley (Hordeum vulgare) genome comprises over 32,000 genes, with differentiated cells expressing only a subset of genes; the remainder being silent. Mechanisms by which tissue-specific genes are regulated are not entirely understood, although DNA methylation is likely to be involved. DNA methylation patterns are not static during plant development, but it is still unclear whether different organs possess distinct methylation profiles. Methylation-sensitive GBS was used to generate DNA methylation profiles for roots, leaf-blades and leaf-sheaths from five barley varieties, using seedlings at the three-leaf stage. Differentially Methylated Markers (DMMs) were characterised by pairwise comparisons of roots, leaf-blades and leaf-sheaths of three different ages. While very many DMMs were found between roots and leaf parts, only a few existed between leaf-blades and leaf-sheaths, with differences decreasing with leaf rank. Organ-specific DMMs appeared to target mainly repeat regions, implying that organ differentiation partially relies on the spreading of DNA methylation from repeats to promoters of adjacent genes. Furthermore, the biological functions of differentially methylated genes in the different organs correlated with functional specialisation. Our results indicate that different organs do possess diagnostic methylation profiles and suggest that DNA methylation is important for both tissue development and differentiation and organ function.

Stage-differentiated modelling of DNA methylation landscapes uncovers salient biomarkers and prognostic signatures in colorectal cancer progression

2021 ◽  
Author(s):  
Sangeetha Muthamilselvan ◽  
Abirami Raghavendran ◽  
Ashok Palaniappan
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Cpg Island ◽  
Early Stage ◽  
P Value ◽  
Consensus Analysis ◽  
One Stage ◽  
Differentially Methylated Genes ◽  
Methylation Patterns ◽  
The Impact

Abstract Background: Aberrant DNA methylation acts epigenetically to skew the gene transcription rate up or down, with causative roles in the etiology of cancers. However research on the role of DNA methylation in driving the progression of cancers is limited. In this study, we have developed a comprehensive computational framework for the stage-differentiated modelling of DNA methylation landscapes in colorectal cancer (CRC), and unravelled significant stagewise signposts of CRC progression. Methods: The methylation β - matrix was derived from the public-domain TCGA data, converted into M-value matrix, annotated with AJCC stages, and analysed for stage-salient genes using multiple approaches involving stage-differentiated linear modelling of methylation patterns and/or expression patterns. Differentially methylated genes (DMGs) were identified using a contrast against controls (adjusted p-value <0.001 and |log fold-change of M-value| >2). These results were filtered using a series of all possible pairwise stage contrasts (p-value <0.05) to obtain stage-salient DMGs. These were then subjected to a consensus analysis, followed by Kaplan–Meier survival analysis to evaluate the impact of methylation patterns of consensus stage-salient biomarkers on disease prognosis.Results: We found significant genome-wide changes in methylation patterns in cancer cases relative to controls agnostic of stage. Our stage-differentiated analysis yielded the following stage-salient genes: one stage-I gene (FBN1), one stage-II gene (FOXG1), one stage-III gene (HCN1) and four stage-IV genes (NELL1, ZNF135, FAM123A, LAMA1). All the biomarkers were hypermethylated, indicating down-regulation and signifying a CpG island Methylator Phenotype (CIMP) manifestation. A significant prognostic signature consisting of FBN1 and FOXG1 survived all the steps of our analysis pipeline, and represents a novel early-stage biomarker. Conclusions: We have designed a workflow for stage-differentiated consensus analysis, and identified stage-salient diagnostic biomarkers and an early-stage prognostic biomarker panel. Our studies further yield a novel CIMP-like signature of potential clinical import underlying CRC progression.

scholarly journals Epigenome-Wide Association Study of Prostate Cancer in African Americans Identifies DNA Methylation Biomarkers for Aggressive Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1826
Author(s):  
Yifan Xu ◽  
Chia-Wen Tsai ◽  
Wen-Shin Chang ◽  
Yuyan Han ◽  
Maosheng Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
African American ◽  
African Americans ◽  
Zinc Finger Protein ◽  
African American Men ◽  
Pathway Enrichment Analysis ◽  
Cpg Sites ◽  
Differentially Methylated Genes ◽  
Incidence And Mortality

DNA methylation plays important roles in prostate cancer (PCa) development and progression. African American men have higher incidence and mortality rates of PCa than other racial groups in U.S. The goal of this study was to identify differentially methylated CpG sites and genes between clinically defined aggressive and nonaggressive PCa in African Americans. We performed genome-wide DNA methylation profiling in leukocyte DNA from 280 African American PCa patients using Illumina MethylationEPIC array that contains about 860K CpG sties. There was a slight increase of overall methylation level (mean β value) with the increasing Gleason scores (GS = 6, GS = 7, GS ≥ 8, P for trend = 0.002). There were 78 differentially methylated CpG sites with P < 10−4 and 9 sites with P < 10−5 in the trend test. We also found 77 differentially methylated regions/genes (DMRs), including 10 homeobox genes and six zinc finger protein genes. A gene ontology (GO) molecular pathway enrichment analysis of these 77 DMRs found that the main enriched pathway was DNA-binding transcriptional factor activity. A few representative DMRs include HOXD8, SOX11, ZNF-471, and ZNF-577. Our study suggests that leukocyte DNA methylation may be valuable biomarkers for aggressive PCa and the identified differentially methylated genes provide biological insights into the modulation of immune response by aggressive PCa.

scholarly journals A research note regarding "Variation in cancer risk among tissues can be explained by the number of stem cell divisions"

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2044
Author(s):  
Maxime Tarabichi ◽  
Vincent Detours
Keyword(s):  
United States ◽  
Hepatocellular Carcinoma ◽  
Stem Cell ◽  
Risk Groups ◽  
The United States ◽  
Prevention Measures ◽  
Cell Divisions ◽  
Hepatocellular Carcinomas ◽  
Major Subset ◽  
Stem Cell Divisions

Tomasetti and Vogelstein argued that 2/3 of human cancers are due to ‘bad luck’ and that “primary prevention measures [against cancer] are not likely to be very effective”. We demonstrate that their calculations for hepatocellular carcinomas overlooked a major subset of these cancers proven to be preventable through vaccination. The problem, which is not limited to hepatocellular carcinoma, arises from the general reliance of their analysis on average incidences in the United States and the omission of incidences in specific risk groups.

scholarly journals Epigenetic aging of human hematopoietic cells is not accelerated upon transplantation into mice

2018 ◽  
Author(s):  
Joana Frobel ◽  
Susann Rahmig ◽  
Julia Franzen ◽  
Claudia Waskow ◽  
Wolfgang Wagner
Keyword(s):  
Dna Methylation ◽  
Epigenetic Clock ◽  
Epigenetic Changes ◽  
Hematopoietic Stem ◽  
Hematopoietic Development ◽  
Immunodeficient Mice ◽  
Epigenetic Aging ◽  
Normal Human ◽  
Methylation Patterns

AbstractTransplantation of human hematopoietic stem cells into immunodeficient mice provides a powerful in vivo model system to gain functional insights into hematopoietic differentiation. So far, it remains unclear if epigenetic changes of normal human hematopoiesis are recapitulated upon engraftment into such “humanized mice”. Mice have a much shorter life expectancy than men, and therefore we hypothesized that the xenogeneic environment might greatly accelerate the epigenetic clock. We demonstrate that genome-wide DNA methylation patterns of normal human hematopoietic development are indeed recapitulated upon engraftment in mice – particularly those of normal early B cell progenitor cells. Furthermore, we tested three epigenetic aging signatures and none of them indicated that the murine environment accelerated age-associated DNA methylation changes. These results demonstrate that the murine transplantation model overall recapitulates epigenetic changes of human hematopoietic development, whereas epigenetic aging seems to occur cell intrinsically.

scholarly journals Integrated Analysis of Methylome and Transcriptome Following Developmental Atrazine Exposure in Zebrafish Reveals Aberrant Gene-Specific Methylation of Neuroendocrine and Reproductive Pathways

2020 ◽  
Author(s):  
Chris Bryan ◽  
Li Lin ◽  
Junkai Xie ◽  
Janiel Ahkin Chin Tai ◽  
Katharine A. Horzmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Molecular Mechanisms ◽  
The United States ◽  
Integrated Analysis ◽  
Aberrant Methylation ◽  
Morphological Alterations ◽  
Differentially Methylated Genes ◽  
Genome Bisulfite Sequencing ◽  
Aberrant Gene

ABSTRACTAtrazine (ATZ) is one of the most commonly used herbicides in the United States. Previous studies have hypothesized the role of ATZ as an endocrine disruptor (EDC), and developmental exposure to ATZ has been shown to lead to behavioral and morphological alterations. Specific epigenetic mechanisms responsible for these alterations, however, are yet to be elucidated. In this study, we exposed zebrafish embryos to 0.3, 3, and 30 ppb (µg/L) of ATZ for 72 hours post fertilization. We performed whole-genome bisulfite sequencing (WGBS) to assess the effects of developmental ATZ exposure on DNA methylation in female fish brains. The number of differentially methylated genes (DMG) increase with increasing dose of treatments. DMGs are enriched in neurological pathways with extensive methylation changes consistently observed in neuroendocrine and reproductive pathways. To assess the effects of DNA methylation on gene expression, we integrated our data with transcriptomic data. Four genes, namely CHD9, FRAS1, PID1, and PCLO, were differentially expressed and methylated in each dose. Overall, this study identifies specific genes and pathways with aberrant methylation and expression following ATZ exposure as targets to elucidate the molecular mechanisms of ATZ toxicity and presents ATZ-induced site-specific DNA methylation as a potential mechanism driving aberrant gene expression.

scholarly journals Neonatal Lead (Pb) Exposure and DNA Methylation Profiles in Dried Bloodspots

2020 ◽  
Vol 17 (18) ◽  
pp. 6775
Author(s):  
Luke Montrose ◽  
Jaclyn M. Goodrich ◽  
Masako Morishita ◽  
Joseph Kochmanski ◽  
Zachary Klaver ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Inductively Coupled Plasma ◽  
Housing Stock ◽  
The United States ◽  
P Value ◽  
Inductively Coupled ◽  
Cpg Sites ◽  
Differentially Methylated Genes ◽  
The World ◽  
Pb Exposure

Lead (Pb) exposure remains a major concern in the United States (US) and around the world, even following the removal of Pb from gasoline and other products. Environmental Pb exposures from aging infrastructure and housing stock are of particular concern to pregnant women, children, and other vulnerable populations. Exposures during sensitive periods of development are known to influence epigenetic modifications which are thought to be one mechanism of the Developmental Origins of Health and Disease (DOHaD) paradigm. To gain insights into early life Pb exposure-induced health risks, we leveraged neonatal dried bloodspots in a cohort of children from Michigan, US to examine associations between blood Pb levels and concomitant DNA methylation profiles (n = 96). DNA methylation analysis was conducted via the Infinium MethylationEPIC array and Pb levels were assessed via high resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). While at-birth Pb exposure levels were relatively low (average 0.78 µg/dL, maximum of 5.27 ug/dL), we identified associations between DNA methylation and Pb at 33 CpG sites, with the majority (82%) exhibiting reduced methylation with increasing Pb exposure (q < 0.2). Biological pathways related to development and neurological function were enriched amongst top differentially methylated genes by p-value. In addition to increases/decreases in methylation, we also demonstrate that Pb exposure is related to increased variability in DNA methylation at 16 CpG sites. More work is needed to assess the accuracy and precision of metals assessment using bloodspots, but this study highlights the utility of this unique resource to enhance environmental epigenetics research around the world.

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