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Cancer epigenomics

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https://www.readbyqxmd.com/read/28445736/systematic-epigenomic-analysis-reveals-chromatin-states-associated-with-melanoma-progression
#1
Petko Fiziev, Kadir C Akdemir, John P Miller, Emily Z Keung, Neha S Samant, Sneha Sharma, Christopher A Natale, Christopher J Terranova, Mayinuer Maitituoheti, Samirkumar B Amin, Emmanuel Martinez-Ledesma, Mayura Dhamdhere, Jacob B Axelrad, Amiksha Shah, Christine S Cheng, Harshad Mahadeshwar, Sahil Seth, Michelle C Barton, Alexei Protopopov, Kenneth Y Tsai, Michael A Davies, Benjamin A Garcia, Ido Amit, Lynda Chin, Jason Ernst, Kunal Rai
The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28444216/dietary-metabolites-derived-from-gut-microbiota-critical-modulators-of-epigenetic-changes-in-mammals
#2
Mohd Iqbal Bhat, Rajeev Kapila
The mammalian gastrointestinal tract harbors trillions of commensal microorganisms, collectively known as the microbiota. The microbiota is a critical source of environmental stimuli and, thus, has a tremendous impact on the health of the host. The microbes within the microbiota regulate homeostasis within the gut, and any alteration in their composition can lead to disorders that include inflammatory bowel disease, allergy, autoimmune disease, diabetes, mental disorders, and cancer. Hence, restoration of the gut flora following changes or imbalance is imperative for the host...
April 22, 2017: Nutrition Reviews
https://www.readbyqxmd.com/read/28442587/combined-aurka-and-h3k9-methyltransferase-targeting-inhibits-cell-growth-by-inducing-mitotic-catastrophe
#3
Angela Mathison, Ann Salmonson, Mckenna Missfeldt, Jennifer Bintz, Monique Williams, Sarah Kossak, Asha Nair, Thiago M de Assuncao, Trace A Christensen, Navtej S Buttar, Juan L Iovanna, Robert Huebert, Gwen Lomberk
The current integrative pathobiological hypothesis states that pancreatic cancer (PDAC) develops and progresses in response to an interaction between known oncogenes and downstream epigenomic regulators. Congruently, this study tests a new combinatorial therapy based on the inhibition of the Aurora kinase A (AURKA) oncogene and one of its targets, the H3K9 methylation-based epigenetic pathway. This therapeutic combination is effective at inhibiting the in vitro growth of PDAC cells both, in monolayer culture systems, and in 3D spheroids and organoids...
April 25, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28442560/obesity-and-menopause-modify-the-epigenomic-profile-of-breast-cancer
#4
Ana B Crujeiras, Angel Díaz-Lagares, Olafur A Stefansson, Manuel Macias, Juan Sandoval, Juan Cueva, Rafael López-López, Sebastian Moran, Jon G Jonasson, Laufey Tryggvadottir, Elinborg Olafsdottir, Francisco J Tinahones, Marcos C Carreira, Felipe F Casanueva, Manel Esteller
Obesity is a high risk factor for breast cancer. This relationship could be marked by a specific methylome. The current work was aimed to explore the impact of obesity and menopausal status on variation in breast cancer methylomes. Data from Infinium 450K array-based methylomes of 64 breast tumor were coupled with information on BMI and menopausal status. Additionally, DNA methylation results were validated in 18 non-tumor and 81 tumor breast samples. Breast tumors arising in either pre- or postmenopausal women stratified by BMI or menopausal status alone were not associated with a specific DNA methylation pattern...
April 25, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28424341/alterations-in-three-dimensional-organization-of-the-cancer-genome-and-epigenome
#5
Joanna Achinger-Kawecka, Phillippa C Taberlay, Susan J Clark
The structural and functional basis of the genome is provided by the three-dimensional (3D) chromatin state. To enable accurate gene regulation, enhancer elements and promoter regions are brought into close spatial proximity to ensure proper, cell type-specific gene expression. In cancer, genetic and epigenetic processes can deregulate the transcriptional program. To investigate whether the 3D chromatin state is also disrupted in cancer we performed Hi-C chromosome conformation sequencing in normal and prostate cancer cells and compared the chromatin interaction maps with changes to the genome and epigenome...
April 19, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28418928/erk-signalling-modulates-epigenome-to-drive-epithelial-to-mesenchymal-transition
#6
Mohit Navandar, Angela Garding, Sanjeeb Kumar Sahu, Abhijeet Pataskar, Sandra Schick, Vijay K Tiwari
The series of events that allow the conversion from adherent epithelial cells into migratory cells is collectively known as epithelial-mesenchymal transition (EMT). EMT is employed during embryonic development such as for gastrulation and neural crest migration and is misused in diseases, such as cancer metastasis. ERK signalling is known to be essential for EMT, however its influence on the epigenetic and transcriptional programme underlying EMT is poorly understood. Here, using a comprehensive genome-wide analysis of H3K27ac mark and gene expression in mammary epithelial cells undergoing EMT, we found that ERK signalling is essential for the epigenetic reprogramming underlying hallmark gene expression and phenotypic changes of EMT...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418867/early-detection-of-gastric-cancer-using-global-genome-wide-and-irf4-elmo1-clip4-and-msc-dna-methylation-in-endoscopic-biopsies
#7
Francesca Pirini, Sassan Noazin, Martha H Jahuira-Arias, Sebastian Rodriguez-Torres, Leah Friess, Christina Michailidi, Jaime Cok, Juan Combe, Gloria Vargas, William Prado, Ethan Soudry, Jimena Pérez, Tikki Yudin, Andrea Mancinelli, Helen Unger, Carmen Ili-Gangas, Priscilla Brebi-Mieville, Douglas E Berg, Masamichi Hayashi, David Sidransky, Robert H Gilman, Rafael Guerrero-Preston
Clinically useful molecular tools to triage gastric cancer patients are not currently available. We aimed to develop a molecular tool to predict gastric cancer risk in endoscopy-driven biopsies obtained from high-risk gastric cancer clinics in low resource settings.We discovered and validated a DNA methylation biomarker panel in endoscopic samples obtained from 362 patients seen between 2004 and 2009 in three high-risk gastric cancer clinics in Lima, Perú, and validated it in 306 samples from the Cancer Genome Atlas project ("TCGA")...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412585/the-promise-of-epigenetic-therapy-reprogramming-the-cancer-epigenome
#8
REVIEW
Andrew D Kelly, Jean-Pierre J Issa
Epigenetics refers to heritable molecular determinants of phenotype independent of DNA sequence. Epigenetic features include DNA methylation, histone modifications, non-coding RNAs, and chromatin structure. The epigenetic status of cells plays a crucial role in determining their differentiation state and proper function within multicellular organisms. Disruption of these processes is now understood to be a major contributor to cancer development and progression, and recent efforts have attempted to pharmacologically reverse such altered epigenetics...
April 13, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28408401/synergistic-immunostimulatory-effects-and-therapeutic-benefit-of-combined-histone-deacetylase-and-bromodomain-inhibition-in-non-small-cell-lung-cancer
#9
Dennis Adeegbe, Yan Liu, Patrick H Lizotte, Yusuke Kamihara, Amir R Aref, Christina Almonte, Ruben Dries, Yuyang Li, Shengwu Liu, Xiaoen Wang, Tiquella Warner-Hatten, Jessica Castrillon, Guo-Cheng Yuan, Neermala Poudel-Neupane, Haikuo Zhang, Jennifer L Guerriero, Shiwei Han, Mark M Awad, David A Barbie, Jerome Ritz, Simon S Jones, Peter S Hammerman, James E Bradner, Steven N Quayle, Kwok-Kin Wong
Effective therapies for non-small cell lung cancer (NSCLC) remain challenging despite an increasingly comprehensive understanding of somatically altered oncogenic pathways. It is now clear that therapeutic agents with potential to impact the tumor immune microenvironment potentiate immune-orchestrated therapeutic benefit. Herein we evaluated the immunoregulatory properties of histone deacetylase (HDAC) and bromodomain inhibitors, two classes of drugs that modulate the epigenome, with a focus on key cell subsets that are engaged in an immune response...
April 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28402164/hijaking-the-epigenome-in-leukemia-and-lymphoma
#10
Amanda C Drennan, Lixin Rui
The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is central to signaling by receptors of diverse cytokines, growth factors, and other related molecules. Many of these receptors transmit anti-apoptosis, proliferation, and differentiation signals that are critical for normal hematopoiesis and immune response. However, the JAK/STAT signaling pathway is deregulated in many hematologic malignancies, and as such is co-opted by malignant cells to promote their survival and proliferation...
April 12, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28400402/molecular-targeted-therapies-in-adrenal-pituitary-and-parathyroid-malignancies
#11
Anna Angelousi, Georgios K Dimitriadis, Gn Zografos, Svenja Nölting, Gregory A Kaltsas, Ashley B Grossman
Tumourigenesis is a relatively common event in endocrine tissues. Currently, specific guidelines have been developed for common malignant endocrine tumours which also incorporate advances in molecular targeted therapies (MTT), as in thyroid cancer and gastrointestinal neuroendocrine malignancies. However, there is little information regarding the role and efficacy of MTT in the relatively rare malignant endocrine tumours mainly involving the adrenal medulla, adrenal cortex, pituitary and parathyroid glands...
April 11, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28400335/review-regulation-of-the-cancer-epigenome-by-long-non-coding-rnas
#12
Megan E Forrest, Ahmad M Khalil
Long non-coding RNAs have emerged as highly versatile players in the regulation of gene expression in development and human disease, particularly cancer. Hundreds of lncRNAs become dysregulated across tumor types, and multiple lncRNAs have demonstrated functions as tumor-suppressors or oncogenes. Furthermore, studies have demonstrated that dysregulation of lncRNAs results in alterations of the epigenome in cancer cells, potentially providing a novel mechanism for the massive epigenomic alterations observed in many tumors...
April 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28396217/mathematical-models-of-cell-phenotype-regulation-and-reprogramming-make-cancer-cells-sensitive-again
#13
David J Wooten, Vito Quaranta
A cell's phenotype is the observable actualization of complex interactions between its genome, epigenome, and local environment. While traditional views in cancer have held that cellular and tumor phenotypes are largely functions of genomic instability, increasing attention has recently been given to epigenetic and microenvironmental influences. Such non-genetic factors allow cancer cells to experience intrinsic diversity and plasticity, and at the tumor level can result in phenotypic heterogeneity and treatment evasion...
April 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28391083/epigenome-wide-association-studies-for-cancer-biomarker-discovery-in-circulating-cell-free-dna-technical-advances-and-challenges
#14
REVIEW
Miljana Tanić, Stephan Beck
Since introducing the concept of epigenome-wide association studies (EWAS) in 2011, there has been a vast increase in the number of published EWAS studies in common diseases, including in cancer. These studies have increased our understanding of epigenetic events underlying carcinogenesis and have enabled the discovery of cancer-specific methylation biomarkers. In this mini-review, we have focused on the state of the art in EWAS applied to cell-free circulating DNA for epigenetic biomarker discovery in cancer and discussed associated technical advances and challenges, and our expectations for the future of the field...
February 16, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28381277/unique-dna-methylation-signature-in-hpv-positive-head-and-neck-squamous-cell-carcinomas
#15
Davide Degli Esposti, Athena Sklias, Sheila C Lima, Stéphanie Beghelli-de la Forest Divonne, Vincent Cahais, Nora Fernandez-Jimenez, Marie-Pierre Cros, Szilvia Ecsedi, Cyrille Cuenin, Liacine Bouaoun, Graham Byrnes, Rosita Accardi, Anne Sudaka, Valérie Giordanengo, Hector Hernandez-Vargas, Luis Felipe Ribeiro Pinto, Ellen Van Obberghen-Schilling, Zdenko Herceg
BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of cancers for which human papilloma virus (HPV) infection is an emerging risk factor. Previous studies showed promoter hypermethylation in HPV(+) oropharyngeal cancers, but only few consistent target genes have been so far described, and the evidence of a functional impact on gene expression is still limited. METHODS: We performed global and stratified pooled analyses of epigenome-wide data in HNSCCs based on the Illumina HumanMethylation450 bead-array data in order to identify tissue-specific components and common viral epigenetic targets in HPV-associated tumours...
April 5, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28378227/epigenetic-approach-for-angiostatic-therapy-promising-combinations-for-cancer-treatment
#16
REVIEW
Robert H Berndsen, U Kulsoom Abdul, Andrea Weiss, Marloes Zoetemelk, Marije T Te Winkel, Paul J Dyson, Arjan W Griffioen, Patrycja Nowak-Sliwinska
Cancer cells are often dependent on epigenetic pathways for their survival. Consequently, drugs that target the epigenome, rather than the underlying DNA sequence, are currently attracting considerable attention. In recent years, the first epigenetic drugs have been approved for cancer chemotherapy, mainly for hematological applications. Limitations in single-drug efficacies have thus far limited their application in the treatment of solid tumors. Nevertheless, promising activity for these compounds has been suggested when combined with other, distinctly targeted agents...
April 4, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28378010/epigenetic-therapy-for-the-treatment-of-epithelial-ovarian-cancer-a-clinical-review
#17
REVIEW
Haller J Smith, J Michael Straughn, Donald J Buchsbaum, Rebecca C Arend
Despite a good initial response to chemotherapy, the majority of patients with epithelial ovarian cancer will eventually recur and die of their disease. The introduction of targeted therapies to traditional chemotherapy regimens has done little to improve overall survival in women with ovarian cancer. It has become increasingly apparent that the cancer epigenome contributes significantly to the pathogenesis of ovarian cancer and may play an important role in cell proliferation, metastasis, chemoresistance, and immune tolerance...
May 2017: Gynecologic Oncology Reports
https://www.readbyqxmd.com/read/28375986/the-new-frontier-of-epigenetic-heterogeneity-in-b-cell-neoplasms
#18
Pilar M Dominguez, Matt Teater, Rita Shaknovich
PURPOSE OF REVIEW: There is mounting evidence that heterogeneity of the epigenome is a feature of many cancers, including B-cell lymphomas, and presents important clinical implications. The purpose of this review is to explain the biological and clinical relevance of this epigenetic phenomenon in B-cell neoplasms. RECENT FINDINGS: Here, we summarize new findings demonstrating that B-cell lymphomas display increased DNA methylation heterogeneity compared to their normal counterparts...
April 1, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28371920/diffuse-intrinsic-pontine-gliomas-current-management-and-new-biologic-insights-is-there-a-glimmer-of-hope
#19
Kenneth J Cohen, Nada Jabado, Jacques Grill
Diffuse intrinsic pontine glioma (DIPG) has proven to be one of the most challenging of all pediatric cancers. Owing to a historical reticence to obtain tumor tissue for study, and based on an erroneous assumption that the biology of DIPG would mirror that of supratentorial high-grade astrocytomas, innumerable studies have been undertaken-all of which have had a negligible impact on the natural history of this disease. More recently, improvements in neurosurgical techniques have allowed for the safe upfront biopsy of DIPG, which, together with a wider use of autopsy tissue, has led to an evolving understanding of the biology of this tumor...
March 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28371392/exercise-and-epigenetic-inheritance-of-disease-risk
#20
REVIEW
Joshua Denham
Epigenetics is the study of gene expression changes that occur in the absence of altered genotype. Current evidence indicates a role for environmentally induced alterations to epigenetic modifications leading to health and diseases changes across multiple generations. This phenomenon is called intergenerational or transgenerational epigenetic inheritance of health or disease. Environmental insults, in the form of toxins, plastics and particular dietary interventions, perturb the epigenetic landscape and influence the health of F1 through to F4 generations in rodents...
March 30, 2017: Acta Physiologica
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