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Cancer epigenomics

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https://www.readbyqxmd.com/read/27924164/smoking-associated-dna-methylation-markers-predict-lung-cancer-incidence
#1
Yan Zhang, Magdeldin Elgizouli, Ben Schöttker, Bernd Holleczek, Alexandra Nieters, Hermann Brenner
BACKGROUND: Newly established blood DNA methylation markers that are strongly associated with smoking might open new avenues for lung cancer (LC) screening. We aimed to assess the performance of the top hits from previous epigenome-wide association studies in prediction of LC incidence. In a prospective nested case-control study, DNA methylation at AHRR (cg05575921), 6p21.33 (cg06126421), and F2RL3 (cg03636183) were measured by pyrosequencing in baseline whole blood samples of 143 incident LC cases identified during 11 years of follow-up and 457 age- and sex-matched controls without diagnosis of LC until the end of follow-up...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27922854/identification-of-hiv-infection-related-dna-methylation-sites-and-advanced-epigenetic-aging-in-hiv-treatment-na%C3%A3-ve-u-s-veterans
#2
Kristin N Nelson, Qin Hui, David Rimland, Ke Xu, Matthew S Freiberg, Amy C Justice, Vincent C Marconi, Yan V Sun
OBJECTIVE: HIV-positive individuals are at higher risk than healthy persons for aging-related diseases, including myocardial infarction and non-AIDS defining cancers. Recent evidence suggests that HIV infection may modulate changes in the host cell epigenome, and these changes represent a potential mechanism through which HIV infection accelerates aging. We assessed the difference in DNAm age, an aging marker involving multiple age-related CpG sites, among antiretroviral treatment (ART) naïve HIV-positive and HIV-negative individuals in a cohort of veterans from the Veterans Aging Cohort Study (VACS)...
December 5, 2016: AIDS
https://www.readbyqxmd.com/read/27917406/genomics-of-colorectal-cancer-in-african-americans
#3
Hassan Brim, Hassan Ashktorab
Genome-wide studies are increasingly becoming a must, especially for complex diseases such as cancer where multiple genes and diverse molecular mechanisms are known to be involved in genes' function alteration. In this review, we report our latest genomic and epigenomic findings in African-American colorectal cancer patients. This population suffers a higher burden of the disease and most investigators in this field are looking for the underlying genetic and epigenetic targets that might be responsible for this disparity...
September 2016: Next Generation, Sequencing & Applications
https://www.readbyqxmd.com/read/27915480/genetic-and-epigenetic-alterations-in-bladder-cancer
#4
REVIEW
Hong-Tao Li, Christopher E Duymich, Daniel J Weisenberger, Gangning Liang
Bladder cancer is one of the most common cancers worldwide, with a high rate of recurrence and poor outcomes as a result of relapse. Bladder cancer patients require lifelong invasive monitoring and treatment, making bladder cancer one of the most expensive malignancies. Lines of evidence increasingly point to distinct genetic and epigenetic alteration patterns in bladder cancer, even between the different stages and grades of disease. In addition, genetic and epigenetic alterations have been demonstrated to play important roles during bladder tumorigenesis...
November 2016: International Neurourology Journal
https://www.readbyqxmd.com/read/27913677/phlpping-through-history-a-decade-in-the-life-of-phlpp-phosphatases
#5
REVIEW
Agnieszka T Grzechnik, Alexandra C Newton
In the decade since their discovery, the PH domain leucine-rich repeat protein phosphatases (PHLPP) have emerged as critical regulators of cellular homeostasis, and their dysregulation is associated with various pathophysiologies, ranging from cancer to degenerative diseases, such as diabetes and heart disease. The two PHLPP isozymes, PHLPP1 and PHLPP2, were identified in a search for phosphatases that dephosphorylate Akt, and thus suppress growth factor signaling. However, given that there are over 200 000 phosphorylated residues in a single cell, and fewer than 50 Ser/Thr protein phosphatases, it is not surprising that PHLPP has many other cellular functions yet to be discovered, including a recently identified role in regulating the epigenome...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27909437/differentially-methylated-dna-regions-in-monozygotic-twin-pairs-discordant-for-rheumatoid-arthritis-an-epigenome-wide-study
#6
Anders J Svendsen, Kristina Gervin, Robert Lyle, Lene Christiansen, Kirsten Kyvik, Peter Junker, Christian Nielsen, Gunnar Houen, Qihua Tan
OBJECTIVES: In an explorative epigenome-wide association study (EWAS) to search for gene independent, differentially methylated DNA positions and regions (DMRs) associated with rheumatoid arthritis (RA) by studying monozygotic (MZ) twin pairs discordant for RA. METHODS: Genomic DNA was isolated from whole blood samples from 28 MZ twin pairs discordant for RA. DNA methylation was measured using the HumanMethylation450 BeadChips. Smoking, anti-cyclic citrullinated peptide antibodies, and immunosuppressive treatment were included as covariates...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27897002/a-methylation-to-expression-feature-model-for-generating-accurate-prognostic-risk-scores-and-identifying-disease-targets-in-clear-cell-kidney-cancer
#7
Jeffrey A Thompson, Carmen J Marsit
Many researchers now have available multiple high-dimensional molecular and clinical datasets when studying a disease. As we enter this multi-omic era of data analysis, new approaches that combine different levels of data (e.g. at the genomic and epigenomic levels) are required to fully capitalize on this opportunity. In this work, we outline a new approach to multi-omic data integration, which combines molecular and clinical predictors as part of a single analysis to create a prognostic risk score for clear cell renal cell carcinoma...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27895805/blood-based-dna-methylation-as-biomarker-for-breast-cancer-a-systematic-review
#8
REVIEW
Qiuqiong Tang, Jie Cheng, Xue Cao, Harald Surowy, Barbara Burwinkel
Multiple studies have investigated global DNA methylation profiles and gene-specific DNA methylation in blood-based DNA to develop powerful screening markers for cancer. This systematic review summarizes the current evidence on methylation studies that investigated methylation level of blood-derived DNA of breast cancer (BC) patients in comparison to healthy controls by conducting a systematic literature review in PubMed and Web of Science. Essential results, such as methylation levels of BC cases and healthy controls, p values, and odds ratios, were extracted from these studies by two investigators independently...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27892767/epigenetic-modifications-in-multiple-myeloma-recent-advances-on-the-role-of-dna-and-histone-methylation
#9
Nicola Amodio, Patrizia D'Aquila, Giuseppe Passarino, Pierfrancesco Tassone, Dina Bellizzi
Multiple Myeloma (MM) is a clonal late B-cell disorder accounting for about 13% of hematological cancers and 1% of all neoplastic diseases. Recent studies on the molecular pathogenesis and biology of MM have highlighted a complex epigenomic landscape contributing to MM onset, prognosis and high individual variability. Areas covered: We describe here the current knowledge on epigenetic events characterizing MM initiation and progression, focusing on the role of DNA and histone methylation and on the most promising epi-therapeutic approaches targeting the methylation pathway...
November 28, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27891192/the-quest-for-an-effective-and-safe-personalized-cell-therapy-using-epigenetic-tools
#10
REVIEW
T A L Brevini, G Pennarossa, E F M Manzoni, C E Gandolfi, A Zenobi, F Gandolfi
In the presence of different environmental cues that are able to trigger specific responses, a given genotype has the ability to originate a variety of different phenotypes. This property is defined as plasticity and allows cell fate definition and tissue specialization. Fundamental epigenetic mechanisms drive these modifications in gene expression and include DNA methylation, histone modifications, chromatin remodeling, and microRNAs. Understanding these mechanisms can provide powerful tools to switch cell phenotype and implement cell therapy...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27889319/cell-type-specific-chromatin-states-differentially-prime-squamous-cell-carcinoma-tumor-initiating-cells-for-epithelial-to-mesenchymal-transition
#11
Mathilde Latil, Dany Nassar, Benjamin Beck, Soufiane Boumahdi, Li Wang, Audrey Brisebarre, Christine Dubois, Erwin Nkusi, Sandrine Lenglez, Agnieszka Checinska, Alizée Vercauteren Drubbel, Michael Devos, Wim Declercq, Rui Yi, Cédric Blanpain
Epithelial to mesenchymal transition (EMT) in cancer cells has been associated with metastasis, stemness, and resistance to therapy. Some tumors undergo EMT while others do not, which may reflect intrinsic properties of their cell of origin. However, this possibility is largely unexplored. By targeting the same oncogenic mutations to discrete skin compartments, we show that cell-type-specific chromatin and transcriptional states differentially prime tumors to EMT. Squamous cell carcinomas (SCCs) derived from interfollicular epidermis (IFE) are generally well differentiated, while hair follicle (HF) stem cell-derived SCCs frequently exhibit EMT, efficiently form secondary tumors, and possess increased metastatic potential...
November 16, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27887572/maternal-smoking-impacts-key-biological-pathways-in-newborns-through-epigenetic-modification-in-utero
#12
Daniel M Rotroff, Bonnie R Joubert, Skylar W Marvel, Siri E Håberg, Michael C Wu, Roy M Nilsen, Per M Ueland, Wenche Nystad, Stephanie J London, Alison Motsinger-Reif
BACKGROUND: Children exposed to maternal smoking during pregnancy exhibit increased risk for many adverse health effects. Maternal smoking influences methylation in newborns at specific CpG sites (CpGs). Here, we extend evaluation of individual CpGs to gene-level and pathway-level analyses among 1062 participants in the Norwegian Mother and Child Cohort Study (MoBa) using the Illumina 450 K platform to measure methylation in newborn DNA and maternal smoking in pregnancy, assessed using the biomarker, plasma cotinine...
November 25, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27885875/epigenomic-therapies-the-potential-of-targeting-sirt6-for-the-treatment-of-pancreatic-cancer
#13
Ihsan Ekin Demir, Güralp O Ceyhan, Helmut Friess
No abstract text is available yet for this article.
November 25, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27865462/molecular-changes-associated-with-tumor-initiation-and-progression-of-soft-tissue-sarcomas-targeting-the-genome-and-epigenome
#14
P W Halcrow, M Dancer, M Panteah, C Walden, J E Ohm
Soft tissue sarcomas are rare, but generally aggressive tumors which disproportionately affect children and young adults. They represent less than 10% of all cancers, but are one of the most frequently diagnosed cancers in pediatric patients. These cancers have a high rate of morbidity and mortality, and their overall incidence has been increasing at an estimated rate of 26% over the last 2 decades. The cause of this increased incidence is unknown but various environmental factors have been implicated. Establishing standard therapeutic strategies is challenging for soft tissue sarcomas as more than 50 different histological subtypes exist, each with their own molecular alterations and clinical characteristics, and this combination of tumor heterogeneity and a limited number of clinical cases make detailed omics level molecular studies particularly challenging...
2016: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/27865461/molecular-and-cellular-changes-during-cancer-progression-resulting-from-genetic-and-epigenetic-alterations
#15
K Pruitt
Tumorigenesis is a complex process that involves a persistent dismantling of cellular safeguards and checkpoints. These molecular and cellular changes that accumulate over months or decades lead to a change in the fundamental identity of a cell as it transitions from normal to malignant. In this chapter, we will examine some of the molecular changes in the evolving relationship between the genome and epigenome and highlight some of the key changes that occur as normal cells progress to tumor cells. For many years tumorigenesis was almost exclusively attributed to mutations in protein-coding genes...
2016: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/27858497/high-fat-diet-and-exercise-lead-to-a-disrupted-and-pathogenic-dna-methylome-in-mouse-liver
#16
Dan Zhou, Ryan A Hlady, Marissa J Schafer, Thomas A White, Chen Liu, Jeong-Hyeon Choi, Jordan D Miller, Lewis R Roberts, Nathan K LeBrasseur, Keith D Robertson
High-fat diet consumption and sedentary life style elevates risk for obesity, non-alcoholic fatty liver disease, and cancer. Exercise training conveys health benefits in populations with or without these chronic conditions. Diet and exercise regulate gene expression by mediating epigenetic mechanisms in many tissues; however, such effects are poorly documented in the liver, a central metabolic organ. To dissect the consequences of diet and exercise on the liver epigenome, we measured DNA methylation, using reduced representation bisulfite sequencing, and transcription, using RNA-seq, in mice maintained on a fast food diet with sedentary lifestyle or exercise, compared to control diet with and without exercise...
November 18, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27855189/genomic-and-transcriptomic-alterations-associated-with-stat3-activation-in-head-and-neck-cancer
#17
Noah D Peyser, Kelsey Pendleton, William E Gooding, Vivian W Y Lui, Daniel E Johnson, Jennifer R Grandis
BACKGROUND: Hyperactivation of STAT3 via constitutive phosphorylation of tyrosine 705 (Y705) is common in most human cancers, including head and neck squamous carcinoma (HNSCC). STAT3 is rarely mutated in cancer and the (epi)genetic alterations that lead to STAT3 activation are incompletely understood. Here we used an unbiased approach to identify genomic and epigenomic changes associated with pSTAT3(Y705) expression using data generated by The Cancer Genome Atlas (TCGA). METHODS AND FINDINGS: Mutation, mRNA expression, promoter methylation, and copy number alteration data were extracted from TCGA and examined in the context of pSTAT3(Y705) protein expression...
2016: PloS One
https://www.readbyqxmd.com/read/27851974/eforge-a-tool-for-identifying-cell-type-specific-signal-in-epigenomic-data
#18
Charles E Breeze, Dirk S Paul, Jenny van Dongen, Lee M Butcher, John C Ambrose, James E Barrett, Robert Lowe, Vardhman K Rakyan, Valentina Iotchkova, Mattia Frontini, Kate Downes, Willem H Ouwehand, Jonathan Laperle, Pierre-Étienne Jacques, Guillaume Bourque, Anke K Bergmann, Reiner Siebert, Edo Vellenga, Sadia Saeed, Filomena Matarese, Joost H A Martens, Hendrik G Stunnenberg, Andrew E Teschendorff, Javier Herrero, Ewan Birney, Ian Dunham, Stephan Beck
Epigenome-wide association studies (EWAS) provide an alternative approach for studying human disease through consideration of non-genetic variants such as altered DNA methylation. To advance the complex interpretation of EWAS, we developed eFORGE (http://eforge.cs.ucl.ac.uk/), a new standalone and web-based tool for the analysis and interpretation of EWAS data. eFORGE determines the cell type-specific regulatory component of a set of EWAS-identified differentially methylated positions. This is achieved by detecting enrichment of overlap with DNase I hypersensitive sites across 454 samples (tissues, primary cell types, and cell lines) from the ENCODE, Roadmap Epigenomics, and BLUEPRINT projects...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27851971/distinct-trends-of-dna-methylation-patterning-in-the-innate-and-adaptive-immune-systems
#19
Ronald P Schuyler, Angelika Merkel, Emanuele Raineri, Lucia Altucci, Edo Vellenga, Joost H A Martens, Farzin Pourfarzad, Taco W Kuijpers, Frances Burden, Samantha Farrow, Kate Downes, Willem H Ouwehand, Laura Clarke, Avik Datta, Ernesto Lowy, Paul Flicek, Mattia Frontini, Hendrik G Stunnenberg, José I Martín-Subero, Ivo Gut, Simon Heath
DNA methylation and the localization and post-translational modification of nucleosomes are interdependent factors that contribute to the generation of distinct phenotypes from genetically identical cells. With 112 whole-genome bisulfite sequencing datasets from the BLUEPRINT Epigenome Project, we analyzed the global development of DNA methylation patterns during lineage commitment and maturation of a range of immune system effector cells and the cancers that arise from them. We show clear trends in methylation patterns that are distinct in the innate and adaptive arms of the human immune system, both globally and in relation to consistently positioned nucleosomes...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27851969/epigenomic-deconvolution-of-breast-tumors-reveals-metabolic-coupling-between-constituent-cell-types
#20
Vitor Onuchic, Ryan J Hartmaier, David N Boone, Michael L Samuels, Ronak Y Patel, Wendy M White, Vesna D Garovic, Steffi Oesterreich, Matt E Roth, Adrian V Lee, Aleksandar Milosavljevic
Cancer progression depends on both cell-intrinsic processes and interactions between different cell types. However, large-scale assessment of cell type composition and molecular profiles of individual cell types within tumors remains challenging. To address this, we developed epigenomic deconvolution (EDec), an in silico method that infers cell type composition of complex tissues as well as DNA methylation and gene transcription profiles of constituent cell types. By applying EDec to The Cancer Genome Atlas (TCGA) breast tumors, we detect changes in immune cell infiltration related to patient prognosis, and a striking change in stromal fibroblast-to-adipocyte ratio across breast cancer subtypes...
November 15, 2016: Cell Reports
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