scholarly journals Blood Surrogate Epigenetic Biomarkers of Atherosclerosis Reveal Common Signature of Inflamm-Aging-Disorders

Proceedings ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 39
Author(s):  
Ken Declerck ◽  
Wim Vanden Berghe
Keyword(s):  
Dna Methylation ◽  
Immune Cell ◽  
Epigenetic Mark ◽  
Epigenetic Clock ◽  
Blood Samples ◽  
Associated Diseases ◽  
Epigenetic Biomarkers ◽  
Cardiometabolic Disorders ◽  
Dna Methylation Profiling ◽  
Methylation Profiling

DNA methylation is the most well-known epigenetic modification of DNA. This epigenetic mark is crucial in controlling gene expression profiles, maintaining cellular identity, genomic imprinting and X-chromosome inactivation. Furthermore, DNA methylation is plastic and can adapt to environmental stimuli, acting as a cellular memory of past events. Whereas epigenetic DNA methylation profiling in cancer diagnostics is now well established, associations with other chronic age-associated diseases, including obesity, diabetes, cardiovascular and neurological diseases have recently started to be explored for prognostic, diagnostic and therapeutic applications. Upon genome-wide DNA methylation profiling of whole blood samples from atherosclerotic patients, we characterized various atherosclerosis specific differentially methylated regions (DMRs). Interestingly, similar DMRs were also observed in other age-and inflammation-associated diseases, like obesity, cancer, Alzheimer’s and Parkinson’s disease, both in blood as well as in brain and tumor tissues. This suggests that inflammaging diseases share a common epigenetic signature of the immune system, which is different from the classic epigenetic clock signature. Furthermore, a cardio-protective flavanol-rich diet intervention can partially reverse this inflammaging disease associated epigenetic pattern. We found that this methylation profile mainly reflects shifts in immune cell type composition and infiltrating immune cell populations. Upon correcting for differences in immune cell composition in blood samples, we identified BRCA1 DNA methylation as an atherosclerosis-specific methylation biomarker irrespective of variations in immune cell biomarkers. How BRCA1 DNA methylation differentially promotes cancer, neurodegeneration or atherosclerosis pathologies requires further investigation. In conclusion, atherosclerosis patient blood samples reveal inflammaging and atherosclerosis-specific DNA methylation biomarkers, which could potentially be used as lifestyle biomarkers to estimate disease risk of neurodegeneration, cardiometabolic disorders and cancer in aging populations.

scholarly journals Meningioma epigenetic grouping reveals biologic drivers and therapeutic vulnerabilities

2020 ◽  
Author(s):  
David Raleigh ◽  
Stephen Magill ◽  
Charlotte Eaton ◽  
Briana Prager ◽  
William Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Methylation ◽  
Central Nervous System ◽  
Nervous System ◽  
Immune Cell ◽  
Lymphatic Vessels ◽  
Intermediate Outcomes ◽  
Dna Methylation Profiling ◽  
New Treatments ◽  
Methylation Profiling

Abstract Meningiomas arising from the meningothelial central nervous system lining are the most common primary intracranial tumors, and a significant cause of neurologic morbidity and mortality1. There are no effective medical therapies for meningioma patients2,3, and new treatments have been encumbered by limited understanding of meningioma biology. DNA methylation profiling provides robust classification of central nervous system tumors4, and can elucidate targets for molecular therapy5. Here we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, and single-cell approaches to show meningiomas are comprised of 3 epigenetic groups with distinct clinical outcomes and biological features informing new treatments for meningioma patients. Merlin-intact meningiomas (group A, 34%) have the best outcomes and are distinguished by a novel apoptotic tumor suppressor function of NF2/Merlin. Immune-enriched meningiomas (group B, 38%) have intermediate outcomes and are distinguished by immune cell infiltration, HLA expression, and lymphatic vessels. Hypermitotic meningiomas (group C, 28%) have the worst outcomes and are distinguished by convergent genetic mechanisms misactivating the cell cycle. Consistently, we find cell cycle inhibitors block meningioma growth in cell culture, organoids, xenografts, and patients. Our results establish a framework for understanding meningioma biology, and provide preclinical rationale for new therapies to treat meningioma patients.

scholarly journals Meningioma epigenetic grouping reveals biologic drivers and therapeutic vulnerabilities

2020 ◽  
Author(s):  
Abrar Choudhury ◽  
Stephen T. Magill ◽  
Charlotte D. Eaton ◽  
Briana C. Prager ◽  
William C. Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Methylation ◽  
Central Nervous System ◽  
Nervous System ◽  
Immune Cell ◽  
Molecular Therapy ◽  
Intermediate Outcomes ◽  
Dna Methylation Profiling ◽  
New Treatments ◽  
Methylation Profiling

SUMMARYMeningiomas arising from the meningothelial central nervous system lining are the most common primary intracranial tumors, and a significant cause of neurologic morbidity and mortality1. There are no effective medical therapies for meningioma patients2,3, and new treatments have been encumbered by limited understanding of meningioma biology. DNA methylation profiling provides robust classification of central nervous system tumors4, and can elucidate targets for molecular therapy5. Here we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, and single-cell approaches to show meningiomas are comprised of 3 epigenetic groups with distinct clinical outcomes and biological features informing new treatments for meningioma patients. Merlin-intact meningiomas (group A, 34%) have the best outcomes and are distinguished by a novel apoptotic tumor suppressor function of NF2/Merlin. Immune-enriched meningiomas (group B, 38%) have intermediate outcomes and are distinguished by immune cell infiltration, HLA expression, and lymphatic vessels. Hypermitotic meningiomas (group C, 28%) have the worst outcomes and are distinguished by convergent genetic mechanisms misactivating the cell cycle. Consistently, we find cell cycle inhibitors block meningioma growth in cell culture, organoids, xenografts, and patients. Our results establish a framework for understanding meningioma biology, and provide preclinical rationale for new therapies to treat meningioma patients.

scholarly journals Assessment of dried blood spots for DNA methylation profiling

2019 ◽  
Vol 4 ◽  
pp. 44 ◽  
Author(s):  
Rosie M. Walker ◽  
Louise MacGillivray ◽  
Sarah McCafferty ◽  
Nicola Wrobel ◽  
Lee Murphy ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Large Scale ◽  
Association Studies ◽  
Disease Onset ◽  
Health Study ◽  
Blood Samples ◽  
Storage Method ◽  
Dna Methylation Profiling ◽  
Edta Tube ◽  
Methylation Profiling

Background: DNA methylation reflects health-related environmental exposures and genetic risk, providing insights into aetiological mechanisms and potentially predicting disease onset, progression and treatment response. An increasingly recognised need for large-scale, longitudinally-profiled samples collected world-wide has made the development of efficient and straightforward sample collection and storage procedures a pressing issue. An alternative to the low-temperature storage of EDTA tubes of venous blood samples, which are frequently the source of the DNA used in such studies, is to collect and store at room temperature blood samples using purpose built filter paper, such as Whatman FTA® cards. Our goal was to determine whether DNA stored in this manner can be used to generate DNA methylation profiles comparable to those generated using blood samples frozen in EDTA tubes. Methods: DNA methylation profiles were obtained from matched EDTA tube and Whatman FTA® card whole-blood samples from 62 Generation Scotland: Scottish Family Health Study participants using the Infinium HumanMethylation450 BeadChip. Multiple quality control procedures were implemented, the relationship between the two sample types assessed, and epigenome-wide association studies (EWASs) performed for smoking status, age and the interaction between these variables and sample storage method. Results: Dried blood spot (DBS) DNA methylation profiles were of good quality and DNA methylation profiles from matched DBS and EDTA tube samples were highly correlated (mean r = 0.991) and could distinguish between participants. EWASs replicated established associations for smoking and age, with no evidence for moderation by storage method. Conclusions: Our results support the use of Whatman FTA® cards for collecting and storing blood samples for DNA methylation profiling. This approach is likely to be particularly beneficial for large-scale studies and those carried out in areas where freezer access is limited. Furthermore, our results will inform consideration of the use of newborn heel prick DBSs for research use.

scholarly journals Assessment of Dried Blood Spots for DNA Methylation Profiling

2019 ◽  
Author(s):  
Rosie M. Walker ◽  
Louise MacGillivray ◽  
Sarah McCafferty ◽  
Nicola Wrobel ◽  
Lee Murphy ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Large Scale ◽  
Smoking Status ◽  
Disease Onset ◽  
Health Study ◽  
Blood Samples ◽  
Storage Method ◽  
Dna Methylation Profiling ◽  
Edta Tube ◽  
Methylation Profiling

AbstractBackgroundDNA methylation reflect health-related environmental exposures and genetic risk, providing insights into aetiological mechanisms and potentially predicting disease onset, progression and treatment response. An increasingly recognised need for large-scale, longitudinally-profiled samples collected world-wide has made the development of efficient and straightforward sample collection and storage procedures a pressing issue. An alternative to the low-temperature storage of EDTA tubes of venous blood samples, which are frequently the source of the DNA used in such studies, is to collect and store at room temperature blood samples using filter paper engineered for the purpose, such as Whatman FTA®cards. Our goal was to determine whether DNA stored in this manner can be used to generate DNA methylation profiles comparable to those generated using blood samples frozen in EDTA tubes.MethodsDNA methylation profiles were obtained from matched EDTA tube and Whatman FTA®card whole-blood samples from 62 Generation Scotland: Scottish Family Health Study participants using the Infinium HumanMethylation450 BeadChip. Multiple quality control procedures were implemented, the relationship between the two sample types assessed, and EWASs performed for smoking status, age and the interaction between these variables and sample storage method. Results: Dried blood spot (DBS) DNA methylation profiles were of good quality and DNA methylation profiles from matched DBS and EDTA tube samples were highly correlated (mean r = 0.991) and could distinguish between participants. EWASs replicated established associations for smoking and age, with no evidence for moderation by storage method.ConclusionsOur results support the use of Whatman FTA®cards for collecting and storing blood samples for DNA methylation profiling. This approach is likely to be particularly beneficial for large-scale studies and those carried out in areas where freezer access is limited. Furthermore, our results will inform consideration of the use of newborn heel prick DBSs for research use.

Forensic DNA methylation profiling from minimal traces: How low can we go?

2018 ◽  
Vol 33 ◽  
pp. 17-23 ◽  
Author(s):  
Jana Naue ◽  
Huub C.J. Hoefsloot ◽  
Ate D. Kloosterman ◽  
Pernette J. Verschure
Keyword(s):  
Dna Methylation ◽  
Forensic Dna ◽  
Dna Methylation Profiling ◽  
Methylation Profiling
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