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Cancer epigenomics

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https://www.readbyqxmd.com/read/28074387/epigenetic-sampling-effects-nephrectomy-modifies-the-clear-cell-renal-cell-cancer-methylome
#1
Christophe Van Neste, Alexander Laird, Fiach O'Mahony, Wim Van Criekinge, Dieter Deforce, Filip Van Nieuwerburgh, Thomas Powles, David J Harrison, Grant D Stewart, Tim De Meyer
PURPOSE: Currently, it is unclear to what extent sampling procedures affect the epigenome. Here, this phenomenon was evaluated by studying the impact of artery ligation on DNA methylation in clear cell renal cancer. METHODS: DNA methylation profiles between vascularised tumour biopsy samples and devascularised nephrectomy samples from two individuals were compared. The relevance of significantly altered methylation profiles was validated in an independent clinical trial cohort...
January 10, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28074068/a-cpg-island-methylator-phenotype-in-acute-myeloid-leukemia-independent-of-idh-mutations-and-associated-with-a-favorable-outcome
#2
A D Kelly, H Kroeger, J Yamazaki, R Taby, F Neumann, S Yu, J T Lee, B Patel, Y Li, R He, S Liang, Y Lu, M Cesaroni, S A Pierce, S M Kornblau, C E Bueso-Ramos, F Ravandi, H M Kantarjian, J Jelinek, J-Pj Issa
Genetic changes are infrequent in acute myeloid leukemia (AML) compared to other malignancies and often involve epigenetic regulators, suggesting that an altered epigenome may underlie AML biology and outcomes. In 96 AML cases including 65 pilot samples selected for cured/not-cured, we found higher CpG island (CGI) promoter methylation in cured patients. Expanded genome-wide digital restriction enzyme analysis of methylation (DREAM) data revealed a CGI methylator phenotype independent of IDH1/2 mutations we term AML-CIMP (A-CIMP(+))...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28070687/predicting-chromatin-architecture-from-models-of-polymer-physics
#3
REVIEW
Simona Bianco, Andrea M Chiariello, Carlo Annunziatella, Andrea Esposito, Mario Nicodemi
We review the picture of chromatin large-scale 3D organization emerging from the analysis of Hi-C data and polymer modeling. In higher mammals, Hi-C contact maps reveal a complex higher-order organization, extending from the sub-Mb to chromosomal scales, hierarchically folded in a structure of domains-within-domains (metaTADs). The domain folding hierarchy is partially conserved throughout differentiation, and deeply correlated to epigenomic features. Rearrangements in the metaTAD topology relate to gene expression modifications: in particular, in neuronal differentiation models, topologically associated domains (TADs) tend to have coherent expression changes within architecturally conserved metaTAD niches...
January 9, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28067913/impaired-h3k36-methylation-defines-a-subset-of-head-and-neck-squamous-cell-carcinomas
#4
Simon Papillon-Cavanagh, Chao Lu, Tenzin Gayden, Leonie G Mikael, Denise Bechet, Christina Karamboulas, Laurie Ailles, Jason Karamchandani, Dylan M Marchione, Benjamin A Garcia, Ilan Weinreb, David Goldstein, Peter W Lewis, Octavia Maria Dancu, Sandeep Dhaliwal, William Stecho, Christopher J Howlett, Joe S Mymryk, John W Barrett, Anthony C Nichols, C David Allis, Jacek Majewski, Nada Jabado
Human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs) are deadly and common cancers. Recent genomic studies implicate multiple genetic pathways, including cell signaling, cell cycle and immune evasion, in their development. Here we analyze public data sets and uncover a previously unappreciated role of epigenome deregulation in the genesis of 13% of HPV-negative HNSCCs. Specifically, we identify novel recurrent mutations encoding p.Lys36Met (K36M) alterations in multiple H3 histone genes...
January 9, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28067867/germline-brca2-mutations-drive-prostate-cancers-with-distinct-evolutionary-trajectories
#5
Renea A Taylor, Michael Fraser, Julie Livingstone, Shadrielle Melijah G Espiritu, Heather Thorne, Vincent Huang, Winnie Lo, Yu-Jia Shiah, Takafumi N Yamaguchi, Ania Sliwinski, Sheri Horsburgh, Alice Meng, Lawrence E Heisler, Nancy Yu, Fouad Yousif, Melissa Papargiris, Mitchell G Lawrence, Lee Timms, Declan G Murphy, Mark Frydenberg, Julia F Hopkins, Damien Bolton, David Clouston, John D McPherson, Theodorus van der Kwast, Paul C Boutros, Gail P Risbridger, Robert G Bristow
Germline mutations in the BRCA2 tumour suppressor are associated with both an increased lifetime risk of developing prostate cancer (PCa) and increased risk of aggressive disease. To understand this aggression, here we profile the genomes and methylomes of localized PCa from 14 carriers of deleterious germline BRCA2 mutations (BRCA2-mutant PCa). We show that BRCA2-mutant PCa harbour increased genomic instability and a mutational profile that more closely resembles metastastic than localized disease. BRCA2-mutant PCa shows genomic and epigenomic dysregulation of the MED12L/MED12 axis, which is frequently dysregulated in metastatic castration-resistant prostate cancer (mCRPC)...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28057210/epigenetic-changes-in-chronic-inflammatory-diseases
#6
O Fogel, C Richard-Miceli, J Tost
The number of people diagnosed with chronic inflammatory diseases has increased noteworthy in the last 40 years. Spondyloarthritis (SpA), inflammatory bowel diseases (IBD), and psoriasis are the most frequent chronic inflammatory diseases, resulting from a combination of genetic predisposition and environmental factors. Epigenetic modifications include DNA methylation, histone modifications, and small and long noncoding RNAs. They are influenced by environmental exposure, life-style, and aging and have recently been shown to be altered in many complex diseases including inflammatory diseases...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28054015/data-on-master-regulators-and-transcription-factor-binding-sites-found-by-upstream-analysis-of-multi-omics-data-on-methotrexate-resistance-of-colon-cancer
#7
AlexanderE Kel
Computational analysis of master regulators through the search for transcription factor binding sites followed by analysis of signal transduction networks of a cell is a new approach of causal analysis of multi-omics data. This paper contains results on analysis of multi-omics data that include transcriptomics, proteomics and epigenomics data of methotrexate (MTX) resistant colon cancer cell line. The data were used for analysis of mechanisms of resistance and for prediction of potential drug targets and promising compounds for reverting the MTX resistance of these cancer cells...
February 2017: Data in Brief
https://www.readbyqxmd.com/read/28052819/disparities-in-cervical-cancer-incidence-and-mortality-can-epigenetics-contribute-to-eliminating-disparities
#8
R L Maguire, A C Vidal, S K Murphy, C Hoyo
Screening for uterine cervical intraepithelial neoplasia (CIN) followed by aggressive treatment has reduced invasive cervical cancer (ICC) incidence and mortality. However, ICC cases and carcinoma in situ (CIS) continue to be diagnosed annually in the United States, with minorities bearing the brunt of this burden. Because ICC peak incidence and mortality are 10-15 years earlier than other solid cancers, the number of potential years of life lost to this cancer is substantial. Screening for early signs of CIN is still the mainstay of many cervical cancer control programs...
2017: Advances in Cancer Research
https://www.readbyqxmd.com/read/28052061/integrated-genomic-characterization-of-oesophageal-carcinoma
#9
(no author information available yet)
Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas...
January 4, 2017: Nature
https://www.readbyqxmd.com/read/28045128/epigenomics-alternations-and-dynamic-transcriptional-changes-in-responses-to-5-fluorouracil-stimulation-reveal-mechanisms-of-acquired-drug-resistance-of-colorectal-cancer-cells
#10
Y Shen, M Tong, Q Liang, Y Guo, H Q Sun, W Zheng, L Ao, Z Guo, F She
A drug-induced resistant cancer cell is different from its parent cell in transcriptional response to drug treatment. The distinct transcriptional response pattern of a drug-induced resistant cancer cell to drug treatment might be introduced by acquired DNA methylation aberration in the cell exposing to sustained drug stimulation. In this study, we performed both transcriptional and DNA methylation profiles of the HCT-8 wild-type cells (HCT-8/WT) for human colorectal cancer (CRC) and the 5-fluorouracil (5-FU)-induced resistant cells (HCT-8/5-FU) after treatment with 5-FU for 0, 24 and 48 h...
January 3, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28013212/organ-specific-epigenetic-changes-induced-by-the-non-genotoxic-liver-carcinogen-methapyrilene-in-fischer-344-rats
#11
Svitlana Shpyleva, Kostiantyn Dreval, Aline de Conti, Iryna Kindrat, Stepan Melnyk, Jian Yan, Tao Chen, Frederick A Beland, Igor P Pogribny
Continuous lifetime exposure to certain natural and man-made chemicals is a major cause of cancers in humans; therefore, evaluating the carcinogenic risks of chemicals remains important. Currently, substantial progress has been made in identification of genotoxic carcinogens; in contrast, predicting a carcinogenic potential of non-genotoxic compounds is a challenge due to many different modes of action that may lead to tumorigenesis. In the present study, we investigated the effects of the non-genotoxic liver carcinogen methapyrilene and the nongenotoxic non-carcinogen usnic acid at doses that do not exhibit organ cytotoxicity on epigenomic alterations in the liver and kidneys of Fischer 344 (F344) rats...
December 24, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28000527/epigenetic-regulation-of-immune-checkpoints-another-target-for-cancer-immunotherapy
#12
Mahmoud A Ali, Marwa Matboli, Marwa Tarek, Maged Reda, Kamal M Kamal, Mahmoud Nouh, Ahmed M Ashry, Ahmed Fath El-Bab, Hend A Mesalam, Ayman El-Sayed Shafei, Omar Abdel-Rahman
Epigenetic changes in oncogenes and tumor-suppressor genes contribute to carcinogenesis. Understanding the epigenetic and genetic components of tumor immune evasion is crucial. Few cancer genetic mutations have been linked to direct correlations with immune evasion. Studies on the epigenetic modulation of the immune checkpoints have revealed a critical interaction between epigenetic and immune modulation. Epigenetic modifiers can activate many silenced genes. Some of them are immune checkpoints regulators that turn on immune responses and others turn them off resulting in immune evasion...
January 2017: Immunotherapy
https://www.readbyqxmd.com/read/27999094/the-epigenetic-landscape-of-alu-repeats-delineates-the-structural-and-functional-genomic-architecture-of-colon-cancer-cells
#13
Mireia Jordà, Anna Díez-Villanueva, Izaskun Mallona, Berta Martín, Sergi Lois, Víctor Barrera, Manel Esteller, Tanya Vavouri, Miguel A Peinado
Cancer cells exhibit multiple epigenetic changes with prominent local DNA hypermethylation and widespread hypomethylation affecting large chromosomal domains. Epigenome studies often disregard the study of repeat elements owing to technical complexity and their undefined role in genome regulation. We have developed NSUMA (Next-generation Sequencing of UnMethylated Alu), a cost-effective approach allowing the unambiguous interrogation of DNA methylation in more than 130,000 individual Alu elements, the most abundant retrotransposon in the human genome...
January 2017: Genome Research
https://www.readbyqxmd.com/read/27997431/attenuation-of-genome-wide-5-methylcytosine-level-is-an-epigenetic-feature-of-cutaneous-malignant-melanomas
#14
Goran Micevic, Nicholas Theodosakis, Janis M Taube, Marcus W Bosenberg, Nemanja Rodić
Epigenetic modification of DNA, namely covalent changes of cytosine residues, plays a key role in the maintenance of inactive chromatin regions, both in health and in disease. In the vast majority of malignant melanomas, the most notable known epigenetic abnormality is the attenuation of 5-hydroxymethylcytosine (5-hmC) residues. However, it remains unknown whether a decrease in 5-hmC represents a primary defect of melanoma cancer epigenome or whether it is secondary to the loss of 5-methylcytosine (5-mC), a chemical substrate for 5-hmC...
December 16, 2016: Melanoma Research
https://www.readbyqxmd.com/read/27989132/dietary-phytochemicals-and-cancer-chemoprevention-a-perspective-on-oxidative-stress-inflammation-and-epigenetics
#15
Wenji Li, Yue Guo, Chengyue Zhang, Renyi Wu, Anne Yuqing Yang, John Gaspar, Ah-Ng Tony Kong
Oxidative stress occurs when cellular reactive oxygen species levels exceed the self-antioxidant capacity of the body. Oxidative stress induces many pathological changes, including inflammation and cancer. Chronic inflammation is believed to be strongly associated with the major stages of carcinogenesis. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a crucial role in regulating oxidative stress and inflammation by manipulating key antioxidant and detoxification enzyme genes via the antioxidant response element...
December 19, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27982729/differential-dna-methylation-and-pm2-5-species-in-a-450k-epigenome-wide-association-study
#16
Lingzhen Dai, Amar Mehta, Irina Mordukhovich, Allan C Just, Jincheng Shen, Lifang Hou, Petros Koutrakis, David Sparrow, Pantel S Vokonas, Andrea A Baccarelli, Joel D Schwartz
Although there is growing evidence that exposure to ambient particulate matter is associated with global DNA methylation and gene-specific methylation, little is known regarding epigenome-wide changes in DNA methylation in relation to particles and, especially, particle components. Using the Illumina Infinium HumanMethylation450 BeadChip, we examined the relationship between one-year moving averages of PM2.5 species (Al, Ca, Cu, Fe, K, Na, Ni, S, Si, V, and Zn) and DNA methylation at 484,613 CpG probes in a longitudinal cohort that included 646 subjects...
December 16, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27980103/repositioning-fda-approved-drugs-in-combination-with-epigenetic-drugs-to-reprogram-colon-cancer-epigenome
#17
Noël J-M Raynal, Elodie M Da Costa, Justin T Lee, Vazganush Gharibyan, Saira Ahmed, Hanghang Zhang, Takahiro Sato, Gabriel G Malouf, Jean-Pierre J Issa
Epigenetic drugs, such as DNA methylation inhibitors (DNMTi) or histone deacetylase inhibitors (HDACi), are approved in monotherapy for cancer treatment. These drugs reprogram gene expression profiles, reactivate tumor suppressor genes (TSG) producing cancer cell differentiation and apoptosis. Epigenetic drugs have been shown to synergize with other epigenetic drugs or various anticancer drugs. To discover new molecular entities that enhance epigenetic therapy, we performed a high-throughput screening using FDA-approved libraries in combination with DNMTi or HDACi...
December 15, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27965295/dna-methylation-derived-neutrophil-to-lymphocyte-ratio-an-epigenetic-tool-to-explore-cancer-inflammation-and-outcomes
#18
Devin C Koestler, Joseph L Usset, Brock C Christensen, Carmen J Marsit, Margaret R Karagas, Karl T Kelsey, John K Wiencke
BACKGROUND: The peripheral blood neutrophil-to-lymphocyte ratio (NLR) is a cytological marker of both inflammation and poor outcomes in cancer patients. DNA methylation is a key element of the epigenetic program defining different leukocyte subtypes and may provide an alternative to cytology in assessing leukocyte profiles. Our aim was to create a bioinformatic tool to estimate NLR using DNA methylation, and to assess its diagnostic and prognostic performance in human populations. METHODS: We developed a DNA methylation-derived NLR (mdNLR) index based on normal isolated leukocyte methylation libraries and established cell-mixture deconvolution algorithms...
December 13, 2016: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27939088/aging-somatic-mutations-epigenetic-drift-and-gene-dosage-imbalance
#19
REVIEW
Reiner A Veitia, Diddahally R Govindaraju, Samuel Bottani, James A Birchler
Aging involves a progressive decline of metabolic function and an increased incidence of late-onset degenerative disorders and cancer. To a large extent, these processes are influenced by alterations affecting the integrity of genome architecture and, ultimately, its phenotypic expression. Despite the progress made towards establishing causal links between genomic and epigenomic changes and aging, mechanisms underlying metabolic dysregulation and age-related phenotypes remain obscure. Here, we present a model linking genome-wide changes and their age-related phenotypic consequences via the alteration of macromolecular complexes and cellular networks...
December 8, 2016: Trends in Cell Biology
https://www.readbyqxmd.com/read/27936926/the-application-of-genome-wide-5-hydroxymethylcytosine-studies-in-cancer-research
#20
John P Thomson, Richard R Meehan
Early detection and characterization of molecular events associated with tumorgenesis remain high priorities. Genome-wide epigenetic assays are promising diagnostic tools, as aberrant epigenetic events are frequent and often cancer specific. The deposition and analysis of multiple patient-derived cancer epigenomic profiles contributes to our appreciation of the underlying biology; aiding the detection of novel identifiers for cancer subtypes. Modifying enzymes and co-factors regulating these epigenetic marks are frequently mutated in cancers, and as epigenetic modifications themselves are reversible, this makes their study very attractive with respect to pharmaceutical intervention...
December 12, 2016: Epigenomics
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