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Cancer epigenomics

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https://www.readbyqxmd.com/read/29774131/methylation-of-dna-and-chromatin-as-a-mechanism-of-oncogenesis-and-therapeutic-target-in-neuroblastoma
#1
REVIEW
Ram Mohan Ram Kumar, Nina Felice Schor
Neuroblastoma (NB), a developmental cancer, is often fatal, emphasizing the need to understand its pathogenesis and identify new therapeutic targets. The heterogeneous pathological and clinical phenotype of NB underscores the cryptic biological and genetic features of this tumor that result in outcomes ranging from rapid progression to spontaneous regression. Despite recent genome-wide mutation analyses, most primary NBs do not harbor driver mutations, implicating epigenetically-mediated gene regulatory mechanisms in the initiation and maintenance of NB...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773832/distinct-epigenetic-landscapes-underlie-the-pathobiology-of-pancreatic-cancer-subtypes
#2
Gwen Lomberk, Yuna Blum, Rémy Nicolle, Asha Nair, Krutika Satish Gaonkar, Laetitia Marisa, Angela Mathison, Zhifu Sun, Huihuang Yan, Nabila Elarouci, Lucile Armenoult, Mira Ayadi, Tamas Ordog, Jeong-Heon Lee, Gavin Oliver, Eric Klee, Vincent Moutardier, Odile Gayet, Benjamin Bian, Pauline Duconseil, Marine Gilabert, Martin Bigonnet, Stephane Garcia, Olivier Turrini, Jean-Robert Delpero, Marc Giovannini, Philippe Grandval, Mohamed Gasmi, Veronique Secq, Aurélien De Reyniès, Nelson Dusetti, Juan Iovanna, Raul Urrutia
Recent studies have offered ample insight into genome-wide expression patterns to define pancreatic ductal adenocarcinoma (PDAC) subtypes, although there remains a lack of knowledge regarding the underlying epigenomics of PDAC. Here we perform multi-parametric integrative analyses of chromatin immunoprecipitation-sequencing (ChIP-seq) on multiple histone modifications, RNA-sequencing (RNA-seq), and DNA methylation to define epigenomic landscapes for PDAC subtypes, which can predict their relative aggressiveness and survival...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29772764/the-making-of-leukemia
#3
REVIEW
Inés González-Herrero, Guillermo Rodríguez-Hernández, Andrea Luengas-Martínez, Marta Isidro-Hernández, Rafael Jiménez, Maria Begoña García-Cenador, Francisco Javier García-Criado, Isidro Sánchez-García, Carolina Vicente-Dueñas
Due to the clonal nature of human leukemia evolution, all leukemic cells carry the same leukemia-initiating genetic lesions, independently of the intrinsic tumoral cellular heterogeneity. However, the latest findings have shown that the mode of action of oncogenes is not homogeneous throughout the developmental history of leukemia. Studies on different types of hematopoietic tumors have shown that the contribution of oncogenes to leukemia is mainly mediated through the epigenetic reprogramming of the leukemia-initiating target cell...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29768164/epigenomic-guided-mass-cytometry-profiling-reveals-disease-specific-features-of-exhausted-cd8-t-cells
#4
Bertram Bengsch, Takuya Ohtani, Omar Khan, Manu Setty, Sasikanth Manne, Shaun O'Brien, Pier Federico Gherardini, Ramin Sedaghat Herati, Alexander C Huang, Kyong-Mi Chang, Evan W Newell, Niels Bovenschen, Dana Pe'er, Steven M Albelda, E John Wherry
Exhausted CD8 T (Tex) cells are immunotherapy targets in chronic infection and cancer, but a comprehensive assessment of Tex cell diversity in human disease is lacking. Here, we developed a transcriptomic- and epigenetic-guided mass cytometry approach to define core exhaustion-specific genes and disease-induced changes in Tex cells in HIV and human cancer. Single-cell proteomic profiling identified 9 distinct Tex cell clusters using phenotypic, functional, transcription factor, and inhibitory receptor co-expression patterns...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29754148/age-prediction-of-children-and-adolescents-aged-6-17-years-an-epigenome-wide-analysis-of-dna-methylation
#5
Chunxiao Li, Wenjing Gao, Ying Gao, Canqing Yu, Jun Lv, Ruoran Lv, Jiali Duan, Ying Sun, Xianghui Guo, Weihua Cao, Liming Li
The DNA methylation age, a good reflection of human aging process, has been used to predict chronological age of adults and newborns. However, the prediction model for children and adolescents was absent. In this study, we aimed to generate a prediction model of chronological age for children and adolescents aged 6-17 years by using age-specific DNA methylation patterns from 180 Chinese twin individuals. We identified 6,350 age-related CpGs from the epigenome-wide association analysis (N=179). 116 known age-related sites in children were confirmed...
May 12, 2018: Aging
https://www.readbyqxmd.com/read/29740925/metformin-directly-targets-the-h3k27me3-demethylase-kdm6a-utx
#6
Elisabet Cuyàs, Sara Verdura, Laura Llorach-Pares, Salvador Fernández-Arroyo, Fedra Luciano-Mateo, Noemí Cabré, Jan Stursa, Lukas Werner, Begoña Martin-Castillo, Benoit Viollet, Jiri Neuzil, Jorge Joven, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Javier A Menendez
Metformin, the first drug chosen to be tested in a clinical trial aimed to target the biology of aging per se, has been clinically exploited for decades in the absence of a complete understanding of its therapeutic targets or chemical determinants. We here outline a systematic chemoinformatics approach to computationally predict biomolecular targets of metformin. Using several structure- and ligand-based software tools and reference databases containing 1,300,000 chemical compounds and more than 9,000 binding sites protein cavities, we identified 41 putative metformin targets including several epigenetic modifiers such as the member of the H3K27me3-specific demethylase subfamily, KDM6A/UTX...
May 8, 2018: Aging Cell
https://www.readbyqxmd.com/read/29739810/the-contributions-of-cancer-cell-metabolism-to-metastasis
#7
REVIEW
Gloria Pascual, Diana Domínguez, Salvador Aznar Benitah
Metastasis remains the leading cause of cancer-related deaths worldwide, and our inability to identify the tumour cells that colonize distant sites hampers the development of effective anti-metastatic therapies. However, with recent research advances we are beginning to distinguish metastasis-initiating cells from their non-metastatic counterparts. Importantly, advances in genome sequencing indicate that the acquisition of metastatic competency does not involve the progressive accumulation of driver mutations; moreover, in the early stages of tumorigenesis, cancer cells harbour combinations of driver mutations that endow them with metastatic competency...
May 3, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29728583/lncrna-oip5-as1-is-overexpressed-in-undifferentiated-oral-tumors-and-integrated-analysis-identifies-as-a-downstream-effector-of-stemness-associated-transcription-factors
#8
Ganesan Arunkumar, Shankar Anand, Partha Raksha, Shankar Dhamodharan, Harikrishnan Prasanna Srinivasa Rao, Shanmugam Subbiah, Avaniyapuram Kannan Murugan, Arasambattu Kannan Munirajan
Long non-coding RNAs (lncRNAs) play an important role in the regulation of key cellular processes in early development and cancer. LncRNA Oip5-as1 facilitates stem cell self-renewal in mouse by sponging mmu-miR-7 and modulating NANOG level, yet its role in cancer is less understood. We analyzed OIP5-AS1 expression in oral tumors and in TCGA datasets. We observed overexpression of OIP5-AS1 in oral tumors (P < 0.001) and in tumors of epithelial origin from TCGA. OIP5-AS1 expression was strongly associated with undifferentiated tumors (P = 0...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29726727/epigenetic-therapy-and-dermatologic-disease-moving-beyond-ctcl
#9
Joshua S Mervis, Jean S McGee
The epigenetic regulation of gene expression is accomplished primarily through DNA methylation, histone modification, and gene silencing via the action of microRNAs. While previously very difficult to study, the field of epigenetics has been greatly facilitated by recent technological innovations. Alterations in the epigenome and epigenetic machinery are now known to be present in a variety of diseases, most notably cancers. Moreover, evidence has emerged that epigenetic dysregulation plays a causative role in disease pathogenesis...
May 4, 2018: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29717273/identification-of-an-episignature-of-human-colorectal-cancer-associated-with-obesity-by-genome-wide-dna-methylation-analysis
#10
Ana B Crujeiras, Sonsoles Morcillo, Angel Diaz-Lagares, Juan Sandoval, Daniel Castellano-Castillo, Esperanza Torres, David Hervas, Sebastian Moran, Manel Esteller, Manuel Macias-Gonzalez, Felipe F Casanueva, Francisco J Tinahones
BACKGROUND: Obesity was established as a relevant modifiable risk factor in the onset and progression of colorectal cancer (CRC). This relationship could be mediated by an epigenetic regulation. OBJECTIVES: The current work aimed to explore the effects of excess body weight on the DNA methylation profile of CRC using a genome-wide DNA methylation approach and to identify an epigenetic signature of obesity-related CRC. METHODS: Fifty-six CRC-diagnosed patients (50 years) were included in the study and categorized according to their body mass index (BMI) as non-obese (BMI ≤ 25 kg/m2 ) or overweight/obese (BMI > 25 kg/m2 )...
May 1, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29713043/epigenome-wide-association-study-of-adiposity-and-future-risk-of-obesity-related-diseases
#11
Gianluca Campanella, Marc J Gunter, Silvia Polidoro, Vittorio Krogh, Domenico Palli, Salvatore Panico, Carlotta Sacerdote, Rosario Tumino, Giovanni Fiorito, Simonetta Guarrera, Licia Iacoviello, Ingvar A Bergdahl, Beatrice Melin, Per Lenner, Theo M C M de Kok, Panagiotis Georgiadis, Jos C S Kleinjans, Soterios A Kyrtopoulos, H Bas Bueno-de-Mesquita, Karen A Lillycrop, Anne M May, N Charlotte Onland-Moret, Robert Murray, Elio Riboli, Monique Verschuren, Eiliv Lund, Nicolle Mode, Torkjel M Sandanger, Valentina Fiano, Morena Trevisan, Giuseppe Matullo, Philippe Froguel, Paul Elliott, Paolo Vineis, Marc Chadeau-Hyam
BACKGROUND: Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction. METHODS: DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework...
May 1, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29712937/galactic-cosmic-radiation-induces-persistent-epigenome-alterations-relevant-to-human-lung-cancer
#12
E M Kennedy, D R Powell, Z Li, J S K Bell, B G Barwick, H Feng, M R McCrary, B Dwivedi, J Kowalski, W S Dynan, K N Conneely, P M Vertino
Human deep space and planetary travel is limited by uncertainties regarding the health risks associated with exposure to galactic cosmic radiation (GCR), and in particular the high linear energy transfer (LET), heavy ion component. Here we assessed the impact of two high-LET ions 56 Fe and 28 Si, and low-LET X rays on genome-wide methylation patterns in human bronchial epithelial cells. We found that all three radiation types induced rapid and stable changes in DNA methylation but at distinct subsets of CpG sites affecting different chromatin compartments...
April 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29697303/2017-michael-fry-award-lecture-when-dna-is-actually-not-a-target-radiation-epigenetics-as-a-tool-to-understand-and-control-cellular-response-to-ionizing-radiation
#13
Igor Koturbash
In addition to the generally accepted potential of ionizing radiation to cause DNA damage, its capability to target the cellular epigenome has become increasingly evident. Epigenetics unifies the chemical marks and molecules that collectively facilitate the proper reading of genetic material. Among the epigenetic mechanisms of regulation, methylation of DNA is known to be the key player in the postirradiation response by controlling the expression of genetic information and activity of transposable elements...
April 26, 2018: Radiation Research
https://www.readbyqxmd.com/read/29693419/a-novel-cell-type-deconvolution-algorithm-reveals-substantial-contamination-by-immune-cells-in-saliva-buccal-and-cervix
#14
Shijie C Zheng, Amy P Webster, Danyue Dong, Andy Feber, David G Graham, Roisin Sullivan, Sarah Jevons, Laurence B Lovat, Stephan Beck, Martin Widschwendter, Andrew E Teschendorff
AIM: An outstanding challenge in epigenome studies is the estimation of cell-type proportions in complex epithelial tissues. MATERIALS & METHODS: Here, we construct and validate a DNA methylation reference and algorithm for complex tissues that contain epithelial, immune and nonimmune stromal cells. RESULTS: Using this reference, we show that easily accessible tissues such as saliva, buccal and cervix exhibit substantial variation in immune cell (IC) contamination...
April 25, 2018: Epigenomics
https://www.readbyqxmd.com/read/29692867/epigenome-wide-dna-methylation-profiling-of-periprostatic-adipose-tissue-in-prostate-cancer-patients-with-excess-adiposity-a-pilot-study
#15
Yan Cheng, Cátia Monteiro, Andreia Matos, Jiaying You, Avelino Fraga, Carina Pereira, Victoria Catalán, Amaia Rodríguez, Javier Gómez-Ambrosi, Gema Frühbeck, Ricardo Ribeiro, Pingzhao Hu
Background: Periprostatic adipose tissue (PPAT) has been recognized to associate with prostate cancer (PCa) aggressiveness and progression. Here, we sought to investigate whether excess adiposity modulates the methylome of PPAT in PCa patients. DNA methylation profiling was performed in PPAT from obese/overweight (OB/OW, BMI > 25 kg m-2 ) and normal weight (NW, BMI < 25 kg m-2 ) PCa patients. Significant differences in methylated CpGs between OB/OW and NW groups were inferred by statistical modeling...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29686738/a-new-approach-to-epigenome-wide-discovery-of-non-invasive-methylation-biomarkers-for-colorectal-cancer-screening-in-circulating-cell-free-dna-using-pooled-samples
#16
María Gallardo-Gómez, Sebastian Moran, María Páez de la Cadena, Vicenta Soledad Martínez-Zorzano, Francisco Javier Rodríguez-Berrocal, Mar Rodríguez-Girondo, Manel Esteller, Joaquín Cubiella, Luis Bujanda, Antoni Castells, Francesc Balaguer, Rodrigo Jover, Loretta De Chiara
Background: Colorectal cancer is the fourth cause of cancer-related deaths worldwide, though detection at early stages associates with good prognosis. Thus, there is a clear demand for novel non-invasive tests for the early detection of colorectal cancer and premalignant advanced adenomas, to be used in population-wide screening programs. Aberrant DNA methylation detected in liquid biopsies, such as serum circulating cell-free DNA (cfDNA), is a promising source of non-invasive biomarkers...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29683440/an-integrated-platform-for-genome-wide-mapping-of-chromatin-states-using-high-throughput-chip-sequencing-in-tumor-tissues
#17
Christopher Terranova, Ming Tang, Elias Orouji, Mayinuer Maitituoheti, Ayush Raman, Samirkumar Amin, Zhiyi Liu, Kunal Rai
Histone modifications constitute a major component of the epigenome and play important regulatory roles in determining the transcriptional status of associated loci. In addition, the presence of specific modifications has been used to determine the position and identity non-coding functional elements such as enhancers. In recent years, chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) has become a powerful tool in determining the genome-wide profiles of individual histone modifications...
April 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29682190/the-jmjn-domain-as-a-dimerization-interface-and-a-targeted-inhibitor-of-kdm4-demethylase-activity
#18
May Levin, Michal Stark, Yehuda G Assaraf
Histone methylation is regulated to shape the epigenome by modulating DNA compaction, thus playing central roles in fundamental chromatin-based processes including transcriptional regulation, DNA repair and cell proliferation. Histone methylation is erased by demethylases including the well-established KDM4 subfamily members, however, little is known about their dimerization capacity and its impact on their demethylase activity. Using the powerful bimolecular fluorescence complementation technique, we herein show the in situ formation of human KDM4A and KDM4C homodimers and heterodimers in nuclei of live transfectant cells and evaluate their H3K9me3 demethylation activity...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29676637/epigenomic-alterations-and-gene-expression-profiles-in-human-respiratory-epithelial-cells-mediated-by-hookah-and-cigarette-smoke
#19
Yin Xiong, Sichuan Xi, Jigui Shan, Elvin Hekimoglu, Shih-Hsin Hsiao, Mary Zhang, Julie A Hong, Chris Tao, Haobin Chen, R Taylor Ripley, Chuong D Hoang, David S Schrump
RATIONALE: The effects of hookah smoke on respiratory epithelia have not been well characterized. OBJECTIVES: To characterize and compare the effects of hookah tobacco smoke and conventional cigarette smoke on the epigenome and transcriptome of human respiratory epithelia. METHODS: Normal human small airway epithelial cells and cyclin-dependent kinase 4/human telomerase reverse transcriptase-immortalized human bronchial epithelial cells were cultured for 5 days in normal media in the presence or absence of water pipe condensates or cigarette smoke condensates under relevant exposure conditions...
April 2018: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29671387/positioning-europe-for-the-epitranscriptomics-challenge
#20
Michael Jantsch, Alessandro Quattrone, Mary O'Connell, Mark Helm, Michaela Frye, Manuel Macias-Gonzales, Marie Ohman, Stefan Ameres, Luc Willems, Francois Fuks, Anastasis Oulas, Stepanka Vanacova, Henrik Nielsen, Cecile Bousquet-Antonelli, Yuri Motorin, Jean-Yves Roignant, Nikolaos Balatsos, Andras Dinnyes, Pavel Baranov, Vincent Kelly, Ayelet Lamm, Gideon Rechavi, Mattia Pelizzola, Janis Liepins, Irina Holodnuka Kholodnyuk, Vanessa Zammit, Duncan Ayers, Finn Drablos, John Arne Dahl, Janusz Bujnicki, Carmen Jeronimo, Raquel Almeida, Monica Neagu, Marieta Costache, Jasna Bankovic, Bojana Banovic, Jan Kyselovic, Luis Miguel Valor, Stefan Selbert, Pinar Pir, Turan Demircan, Victoria Cowling, Matthias Schäfer, Walter Rossmanith, Denis Lafontaine, Alexandre David, Clement Carre, Frank Lyko, Raffael Schaffrath, Schraga Schwartz, Andre Verdel, Arne Klungland, Elzbieta Purta, Gordana Timotijevic, Fernando Cardona, Alberto Davalos, Ester Ballana, Donal O Carroll, Jernej Ule, Rupert Fray
The genetic alphabet consists of the four letters: C, A, G, and T in DNA and C,A,G, and U in RNA. Triplets of these four letters jointly encode 20 different amino acids out of which proteins of all organisms are built. This system is universal and is found in all kingdoms of life. However, bases in DNA and RNA can be chemically modified. In DNA, around 10 different modifications are known, and those have been studied intensively over the past 20 years. Scientific studies on DNA modifications and proteins that recognize them gave rise to the large field of epigenetic and epigenomic research...
April 19, 2018: RNA Biology
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