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Cancer AND epigenom

Jay F Sarthy, Steven Henikoff, Kami Ahmad
Cancer accounts for ∼9 million deaths per year worldwide, predominantly affecting adults. Adult malignancies are usually examined after extensive clonal evolution and carry many mutations, obscuring the individual contributions of these alterations to oncogenesis. By contrast, pediatric cancers often contain few mutations, many of which cause defects in chromatin-associated proteins. We explore here the roles that chromatin plays in oncogenesis. We highlight how the developmental regulation of cell proliferation genes and the degradation of chromosome ends are two major bottlenecks in the evolution of malignant cells, and point to a third bottleneck where epigenomic dysfunction triggers expression of tumor-suppressor genes, limiting the development of aggressive and metastatic features in tumors...
March 2019: Trends in Cancer
Emma Scott, Jennifer Munkley
Prostate cancer is the most commonly diagnosed malignancy in men, claiming over350,000 lives worldwide annually. Current diagnosis relies on prostate-specific antigen (PSA)testing, but this misses some aggressive tumours, and leads to the overtreatment of non-harmfuldisease. Hence, there is an urgent unmet clinical need to identify new diagnostic and prognosticbiomarkers. As prostate cancer is a heterogeneous and multifocal disease, it is likely that multiplebiomarkers will be needed to guide clinical decisions...
March 19, 2019: International Journal of Molecular Sciences
Tatsuo Kanda, Taichiro Goto, Yosuke Hirotsu, Mitsuhiko Moriyama, Masao Omata
Almost all patients with hepatocellular carcinoma (HCC), a major type of primary liver cancer, also have liver cirrhosis, the severity of which hampers effective treatment for HCC despite recent progress in the efficacy of anticancer drugs for advanced stages of HCC. Here, we review recent knowledge concerning the molecular mechanisms of liver cirrhosis and its progression to HCC from genetic and epigenomic points of view. Because ~70% of patients with HCC have hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection, we focused on HBV- and HCV-associated HCC...
March 18, 2019: International Journal of Molecular Sciences
Ankit Sinha, Vincent Huang, Julie Livingstone, Jenny Wang, Natalie S Fox, Natalie Kurganovs, Vladimir Ignatchenko, Katharina Fritsch, Nilgun Donmez, Lawrence E Heisler, Yu-Jia Shiah, Cindy Q Yao, Javier A Alfaro, Stas Volik, Anna Lapuk, Michael Fraser, Ken Kron, Alex Murison, Mathieu Lupien, Cenk Sahinalp, Colin C Collins, Bernard Tetu, Mehdi Masoomian, David M Berman, Theodorus van der Kwast, Robert G Bristow, Thomas Kislinger, Paul C Boutros
DNA sequencing has identified recurrent mutations that drive the aggressiveness of prostate cancers. Surprisingly, the influence of genomic, epigenomic, and transcriptomic dysregulation on the tumor proteome remains poorly understood. We profiled the genomes, epigenomes, transcriptomes, and proteomes of 76 localized, intermediate-risk prostate cancers. We discovered that the genomic subtypes of prostate cancer converge on five proteomic subtypes, with distinct clinical trajectories. ETS fusions, the most common alteration in prostate tumors, affect different genes and pathways in the proteome and transcriptome...
March 18, 2019: Cancer Cell
Andrea G Izquierdo, Ana B Crujeiras
The prevalence of insulin resistance (IR) is increasing rapidly worldwide and it is a relevant health problem because it is associated with several diseases, such as type 2 diabetes, cardiovascular disorders and cancer. Understanding the mechanisms involved in IR onset and progression will open new avenues for identifying biomarkers for preventing and treating IR and its co-diseases. Epigenetic mechanisms such as DNA methylation are important factors that mediate the environmental effect in the genome by regulating gene expression and consequently its effect on the phenotype and the development of disease...
March 18, 2019: Reviews in Endocrine & Metabolic Disorders
Jawara Allen, Stephanie Hao, Cynthia L Sears, Winston Timp
Enterotoxigenic Bacteroides fragilis (ETBF) is a gram negative, obligate anaerobe member of the gut microbial community in up to 40% of healthy individuals. This bacterium is found more frequently in people with colorectal cancer (CRC) and causes tumor formation in the distal colon of Apc min/+ mice; tumor formation is dependent on ETBF-secreted Bacteroides fragilis toxin (BFT). Because of the extensive data connecting alterations in the epigenome with tumor formation, initial experiments attempting to connect BFT-induced tumor formation with methylation in colon epithelial cells (CECs) have been performed, but the effect of BFT on other epigenetic processes, such as chromatin structure, remains unexplored...
March 18, 2019: Infection and Immunity
Qing-Lan Li, Dan-Ya Wang, Lin-Gao Ju, Jie Yao, Chuan Gao, Pin-Ji Lei, Lian-Yun Li, Xiao-Lu Zhao, Min Wu
BACKGROUND: Activation of transcription enhancers, especially super-enhancers, is one of the critical epigenetic features of tumorigenesis. However, very few studies have systematically identified the enhancers specific in cancer tissues. METHODS: Here, we studied the change of histone modifications in MMTV-PyVT breast cancer model, combining mass spectrometry-based proteomics and ChIP-seq-based epigenomics approaches. Some of the proteomic results were confirmed with western blotting and IHC staining...
March 12, 2019: Clinical Epigenetics
Bo Zhou, Steve S Ho, Stephanie U Greer, Noah Spies, John M Bell, Xianglong Zhang, Xiaowei Zhu, Joseph G Arthur, Seunggyu Byeon, Reenal Pattni, Ishan Saha, Yiling Huang, Giltae Song, Dimitri Perrin, Wing H Wong, Hanlee P Ji, Alexej Abyzov, Alexander E Urban
HepG2 is one of the most widely used human cancer cell lines in biomedical research and one of the main cell lines of ENCODE. Although the functional genomic and epigenomic characteristics of HepG2 are extensively studied, its genome sequence has never been comprehensively analyzed and higher order genomic structural features are largely unknown. The high degree of aneuploidy in HepG2 renders traditional genome variant analysis methods challenging and partially ineffective. Correct and complete interpretation of the extensive functional genomics data from HepG2 requires an understanding of the cell line's genome sequence and genome structure...
March 13, 2019: Nucleic Acids Research
Daniel C Turner, Robert A Seaborne, Adam P Sharples
Transcriptome wide changes in human skeletal muscle after acute (anabolic) and chronic resistance exercise (RE) induced hypertrophy have been extensively determined in the literature. We have also recently undertaken DNA methylome analysis (850,000 + CpG sites) in human skeletal muscle after acute and chronic RE, detraining and retraining, where we identified an association between DNA methylation and epigenetic memory of exercise induced skeletal muscle hypertrophy. However, it is currently unknown as to whether all the genes identified in the transcriptome studies to date are also epigenetically regulated at the DNA level after acute, chronic or repeated RE exposure...
March 12, 2019: Scientific Reports
Lorenza Rimassa, Nicola Personeni, Alessio Aghemo, Ana Lleo
Cholangiocarcinoma (CCA) is a deadly cancer of the biliary epithelium with limited therapeutic options. It is a heterogeneous group of cancer that could develop at any level from the biliary tree and is currently classified into intrahepatic, perihilar and distal based on its anatomical location. With incidence and mortality rates currently increasing, it is now the second most common type of primary liver cancer and represents up to 3% of all gastrointestinal malignancies. High-throughput genomics and epigenomics have greatly increased our understanding of CCA underlying biology, however its pathogenesis remains largely unknown...
March 9, 2019: Journal of Autoimmunity
Konstantinos Dimopoulos, Kirsten Grønbaek
The increasing depth of knowledge about cancer biology throughout the last decades, has underlined the importance of not only genetic aberrations, but also epigenetic abnormalities in cancer cells. The extensive exploration of the cancer epigenome has provided insights into key pathways involved in tumorigenesis, as well as has allowed the development of novel epigenetic therapies. In this review, we will present the important role of epigenetic alterations in hematological diseases, with special focus on epigenetically-based targeting of hematological malignancies...
March 12, 2019: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
Jack Hearn, Marianne Pearson, Mark Blaxter, Philip J Wilson, Tom J Little
BACKGROUND: The degradation of epigenetic control with age is associated with progressive diseases of ageing, including cancers, immunodeficiency and diabetes. Reduced caloric intake slows the effects of ageing and age-related disease in vertebrates and invertebrates, a process potentially mediated by the impact of caloric restriction on epigenetic factors such as DNA methylation. We used whole genome bisulphite sequencing to study how DNA methylation patterns change with diet in a small invertebrate, the crustacean Daphnia magna...
March 8, 2019: BMC Genomics
Neha Bunkar, Ruchita Shandilya, Arpit Bhargava, Ravindra M Samarth, Rajnarayan Tiwari, Dinesh Kumar Mishra, Rupesh Kumar Srivastava, Radhey Shyam Sharma, Nirmal Kumar Lohiya, Pradyumna Kumar Mishra
Diet and environment are two critical regulators that influence an individual's epigenetic profile. Besides the anterograde signaling, mitochondria act as a key regulator of epigenetic alterations in cancer either by controlling the concentration of the cofactors, activity of vital enzymes or by affecting the transcription of NF-kappaB and associated signaling molecules. As epigenetic modifications are the major drivers of aberrant gene expression, designing novel nutri-epigenomic strategies to modulate reversible epigenetic modifications will be important for effective cancer protection...
March 1, 2019: Frontiers in Bioscience (Landmark Edition)
Emma Cazaly, Joseph Saad, Wenyu Wang, Caroline Heckman, Miina Ollikainen, Jing Tang
Epigenetic research involves examining the mitotically heritable processes that regulate gene expression, independent of changes in the DNA sequence. Recent technical advances such as whole-genome bisulfite sequencing and affordable epigenomic array-based technologies, allow researchers to measure epigenetic profiles of large cohorts at a genome-wide level, generating comprehensive high-dimensional datasets that may contain important information for disease development and treatment opportunities. The epigenomic profile for a certain disease is often a result of the complex interplay between multiple genetic and environmental factors, which poses an enormous challenge to visualize and interpret these data...
2019: Frontiers in Pharmacology
Sophia Harlid, Zongli Xu, Erin Kirk, Lauren E Wilson, Melissa A Troester, Jack A Taylor
Hormone therapy (HT) is associated with increased risk of breast cancer, strongly dependent on type, duration, and recency of use. HT use could affect cancer risk by changing breast tissue transcriptional programs. We hypothesize that these changes are preceded by changes in DNA methylation. To explore this hypothesis we used histologically normal-appearing breast tissue from the Normal Breast Study (NBS). DNA methylation β-values were obtained using the Illumina HumanMethylation 450 BeadChips for 90 samples including all NBS-participants who used HT within 5 y before surgery...
March 1, 2019: Epigenetics: Official Journal of the DNA Methylation Society
Shangwei Zhong, Cuiping Li, Xiao Han, Xiangjun Li, Yungui Yang, Hailin Wang
The topoisomerase II inhibitor idarubicin (Ida) is an effective anti-cancer anthracycline drug and has been used for clinical therapies of multiple cancers. It is well-known that Ida and its analogues can induce DNA double strand breakage (DSB) by inhibiting topoisomer II and kill tumor cells. To date, it remains unknown whether they alter DNA epigenomes. Here, we show that Ida significantly stimulates the oxidation of a key epigenetic mark DNA 5-methyl-2'-deoxycytidine (5mC), resulting in elevation of 5-hydroxymethyl-2'-deoxycytidine (5hmC) in four tested cell lines...
February 28, 2019: Chemical Research in Toxicology
Ivan V Zmitrovich, Nina V Belova, Mikhail E Balandaykin, Margarita A Bondartseva, Solomon P Wasser
In this review we outline a framework in which mycotherapy is effective in the field of oncology. We suppose that irreversible epigenomic changes in cancer cells and achieving their replicative immortality when cancer-specific targets are absent should take away any illusions about a fundamental possibility of pharmacological blockage of the cancer process once ontogenesis begins. At the same time, however, we believe that effects of both traditional and alternative medicines on cancer clonogenic units within a particular range can lead to prolonged remission; with this in mind, we carefully consider the various possibilities of mycotherapy in controlling cancer activity...
2019: International Journal of Medicinal Mushrooms
Jawara Allen, Cynthia L Sears
In recent years, the number of studies investigating the impact of the gut microbiome in colorectal cancer (CRC) has risen sharply. As a result, we now know that various microbes (and microbial communities) are found more frequently in the stool and mucosa of individuals with CRC than healthy controls, including in the primary tumors themselves, and even in distant metastases. We also know that these microbes induce tumors in various mouse models, but we know little about how they impact colon epithelial cells (CECs) directly, or about how these interactions might lead to modifications at the genetic and epigenetic levels that trigger and propagate tumor growth...
February 25, 2019: Genome Medicine
Visakh R, K A Abdul Nazeer
BACKGROUND AND OBJECTIVE: High-throughput Next Generation Sequencing tools have generated immense quantity of genome-wide methylation and expression profiling data, resulting in an unprecedented opportunity to unravel the epigenetic regulatory mechanisms underlying cancer. Identifying differentially methylated regions within gene networks is an important step towards revealing the cancer epigenome blueprint. Approaches that integrate gene methylation and expression profiles assume their negative correlation and build a single scaffold network to cluster...
February 21, 2019: Gene
Joshua Rowland, Artur Akbarov, James Eales, Xiaoguang Xu, John P Dormer, Hui Guo, Matthew Denniff, Xiao Jiang, Parisa Ranjzad, Alicja Nazgiewicz, Priscilla Ribeiro Prestes, Andrzej Antczak, Monika Szulinska, Ingrid A Wise, Ewa Zukowska-Szczechowska, Pawel Bogdanski, Adrian S Woolf, Nilesh J Samani, Fadi J Charchar, Maciej Tomaszewski
Nephrons scar and involute during aging, increasing the risk of chronic kidney disease. Little is known, however, about genetic mechanisms of kidney aging. We sought to define the signatures of age on the renal transcriptome using 563 human kidneys. The initial discovery analysis of 260 kidney transcriptomes from the TRANScriptome of renaL humAn TissuE Study (TRANSLATE) and the Cancer Genome Atlas identified 37 age-associated genes. For 19 of those genes, the association with age was replicated in 303 kidney transcriptomes from the Nephroseq resource...
March 2019: Kidney International
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