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Cancer AND epigenom

Lauren Lewis, Grace A Chappell, Tetyana Kobets, Bridget E O'Brian, Dewakar Sangaraju, Oksana Kosyk, Wanda Bodnar, Natalia Y Tretyakova, Igor P Pogribny, Ivan Rusyn
Exposure to environmental chemicals has been shown to have an impact on the epigenome. One example is a known human carcinogen 1,3-butadiene which acts primarily by a genotoxic mechanism, but also disrupts the chromatin structure by altering patterns of cytosine DNA methylation and histone modifications. Sex-specific differences in 1,3-butadiene-induced genotoxicity and carcinogenicity are well established; however, it remains unknown whether 1,3-butadiene-associated epigenetic alterations are also sex dependent...
December 14, 2018: Archives of Toxicology
Madeleine A Young, Stephanie May, Angelos Damo, Young So Yoon, Man-Wook Hur, Wojciech Swat, Lee Parry
Both alterations to the epigenome and loss of polarity have been linked to cancer initiation, progression and metastasis. It has previously been demonstrated that loss of the epigenetic reader protein Kaiso suppresses intestinal tumourigenesis in the Apc+/min mouse model, in which altered polarity plays a key role. Thus, we investigated the link between Kaiso deficiency, polarity and suppression of intestinal tumourigenesis. We used Kaiso deficient mice to conditionally delete Apc within the intestinal epithelia and demonstrated up-regulation of the spindle polarity genes Dlg1 and Dlgap1...
December 14, 2018: Molecular Cancer Research: MCR
Lingfang Feng, Jianlin Lou
DNA methylation is a process by which methyl groups are added to cytosine or adenine. DNA methylation can change the activity of the DNA molecule without changing the sequence. Methylation of 5-methylcytosine (5mC) is widespread in both eukaryotes and prokaryotes, and it is a very important epigenetic modification event, which can regulate gene activity and influence a number of key processes such as genomic imprinting, cell differentiation, transcriptional regulation, and chromatin remodeling. Profiling DNA methylation across the genome is critical to understanding the influence of methylation in normal biology and diseases including cancer...
2019: Methods in Molecular Biology
Feda H Hamdan, Steven A Johnsen
Molecular subtyping of cancer offers tremendous promise for the optimization of a precision oncology approach to anticancer therapy. Recent advances in pancreatic cancer research uncovered various molecular subtypes with tumors expressing a squamous/basal-like gene expression signature displaying a worse prognosis. Through unbiased epigenome mapping, we identified deltaNp63 as a major driver of a gene signature in pancreatic cancer cell lines, which we report to faithfully represent the highly aggressive pancreatic squamous subtype observed in vivo, and display the specific epigenetic marking of genes associated with decreased survival...
December 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Renata L Markman, Liana P Webber, Carlos H V Nascimento Filho, Leonardo A Reis, Pablo A Vargas, Marcio A Lopes, Virgilio Zanella, Manoela D Martins, Cristiane H Squarize, Rogerio M Castilho
PURPOSE: Emerging evidence indicates that bromodomains comprise a conserved class of epigenome readers involved in cancer development and inflammation. Bromodomains are associated with epigenetic modifications of gene transcription through interactions with lysine residues of histone tails. Particularly, the bromodomain and extra-terminal domain (BET) family member BRD4 has been found to be involved in the control over oncogenes, including c-MYC, and in the maintenance of downstream inflammatory processes...
December 11, 2018: Cellular Oncology (Dordrecht)
Santiago Lascano, Marie Lopez, Paola B Arimondo
DNA methylation and histone acetylation are widely studied epigenetic modifications. They are involved in numerous pathologies such as cancer, neurological disease, inflammation, obesity, etc. Since the discovery of the epigenome, numerous compounds have been developed to reverse DNA methylation and histone acetylation aberrant profile in diseases. Among them several were inspired by Nature and have a great interest as therapeutic molecules. In the quest of finding new ways to target epigenetic mechanisms, the use of chemical tools is a powerful strategy to better understand epigenetic mechanisms in biological systems...
December 2018: Chemical Record: An Official Publication of the Chemical Society of Japan ... [et Al.]
Yusuke Okuma, Kei Morikawa, Hisashi Tanaka, Takuma Yokoyama, Hidetoshi Itani, Kazuya Horiuchi, Hideyuki Nakagawa, Nobumasa Takahashi, Akihiro Bessho, Kenzo Soejima, Kazuma Kishi, Akira Togashi, Yae Kanai, Koji Ueda, Katsuhisa Horimoto, Noriyuki Matsutani, Nobuhiko Seki
Patients with EGFR-mutated non-small cell lung cancer (NSCLC) exhibit resistance to EGFR-tyrosine kinase inhibitors (TKIs) within 9-14 months of therapy. Recently, EGFR-mutated NSCLC has demonstrated the potential for heterogeneity; therefore, the manner of clonal heterogeneity may impact the duration of progression-free and overall survival and other parameters affecting EGFR-TKI treatment efficacy. However no predictive biomarker of these favorable treatment efficacies has been identified to date. The exosome-focused translational research for afatinib (EXTRA) study aims to identify a novel predictive biomarker and a resistance marker for afatinib by analyzing data from association studies of the clinical efficacy of afatinib and four "OMICs" (genomics, proteomics, epigenomics, and metabolomics) using peripheral blood from patients treated with afatinib...
December 8, 2018: Thoracic Cancer
Shirin Golabi Aghdam, Mehrdad Ebrazeh, Maryam Hemmatzadeh, Narges Seyfizadeh, Arezoo Gowhari Shabgah, Gholamreza Azizi, Negin Ebrahimi, Farhad Babaie, Hamed Mohammadi
Prostate cancer (PCa) is considered the most prevalent malignancy and the second major cause of cancer-related death in males from Western countries. PCa exhibits variable clinical pictures, ranging from dormant to highly metastatic cancer. PCa suffers from poor prognosis and diagnosis markers, and novel biomarkers are required to define disease stages and to design appropriate therapeutic approach by considering the possible genomic and epigenomic differences. MicroRNAs (miRNAs) comprise a class of small noncoding RNAs, which have remarkable functions in cell formation, differentiation, and cancer development and contribute in these processes through controlling the expressions of protein-coding genes by repressing translation or breaking down the messenger RNA in a sequence-specific method...
December 7, 2018: Journal of Cellular Physiology
Charu Aggarwal, Steven M Albelda
Malignant pleural mesothelioma (MPM) is an aggressive lethal malignancy for which very few therapeutic options exist. In this issue of Cancer Discovery , Hmeljak and colleagues report on a comprehensive integrative analysis of histology-independent genomic characteristics of MPM. They confirm previous observations that inactivation of tumor suppressor genes is the predominant oncogenic mechanism. This study provides a scientific rationale for potentially novel therapeutic options, including immune-checkpoint targeting VISTA and small-molecule inhibitors targeting the epigenome, DNA-repair pathways, and aurora kinase...
December 2018: Cancer Discovery
Xianwen Ren, Boxi Kang, Zemin Zhang
Cellular heterogeneity within and across tumors has been a major obstacle in understanding and treating cancer, and the complex heterogeneity is masked if bulk tumor tissues are used for analysis. The advent of rapidly developing single-cell sequencing technologies, which include methods related to single-cell genome, epigenome, transcriptome, and multi-omics sequencing, have been applied to cancer research and led to exciting new findings in the fields of cancer evolution, metastasis, resistance to therapy, and tumor microenvironment...
December 3, 2018: Genome Biology
Stephin J Vervoort, Olivier G de Jong, M Guy Roukens, Cynthia L Frederiks, Jeroen F Vermeulen, Ana Rita Lourenço, Laura Bella, Ana Tufegdzic Vidakovic, José L Sandoval, Cathy Moelans, Miranda van Amersfoort, Margaret J Dallman, Alejandra Bruna, Carlos Caldas, Edward Nieuwenhuis, Elsken van der Wall, Patrick Derksen, Paul van Diest, Marianne C Verhaar, Eric W-F Lam, Michal Mokry, Paul J Coffer
The expression of the transcription factor SOX4 is increased in many human cancers, however, the pro-oncogenic capacity of SOX4 can vary greatly depending on the type of tumor. Both the contextual nature and the mechanisms underlying the pro-oncogenic SOX4 response remain unexplored. Here, we demonstrate that in mammary tumorigenesis, the SOX4 transcriptional network is dictated by the epigenome and is enriched for pro-angiogenic processes. We show that SOX4 directly regulates endothelin-1 (ET-1) expression and can thereby promote tumor-induced angiogenesis both in vitro and in vivo...
December 3, 2018: ELife
Shijie C Zheng, Charles E Breeze, Stephan Beck, Andrew E Teschendorff
An outstanding challenge of epigenome-wide association studies (EWASs) performed in complex tissues is the identification of the specific cell type(s) responsible for the observed differential DNA methylation. Here we present a statistical algorithm called CellDMC ( ), which can identify differentially methylated positions and the specific cell type(s) driving the differential methylation. We validated CellDMC on in silico mixtures of DNA methylation data generated with different technologies, as well as on real mixtures from epigenome-wide association and cancer epigenome studies...
December 2018: Nature Methods
Shuhui Bian, Yu Hou, Xin Zhou, Xianlong Li, Jun Yong, Yicheng Wang, Wendong Wang, Jia Yan, Boqiang Hu, Hongshan Guo, Jilian Wang, Shuai Gao, Yunuo Mao, Ji Dong, Ping Zhu, Dianrong Xiu, Liying Yan, Lu Wen, Jie Qiao, Fuchou Tang, Wei Fu
Although genomic instability, epigenetic abnormality, and gene expression dysregulation are hallmarks of colorectal cancer, these features have not been simultaneously analyzed at single-cell resolution. Using optimized single-cell multiomics sequencing together with multiregional sampling of the primary tumor and lymphatic and distant metastases, we developed insights beyond intratumoral heterogeneity. Genome-wide DNA methylation levels were relatively consistent within a single genetic sublineage. The genome-wide DNA demethylation patterns of cancer cells were consistent in all 10 patients whose DNA we sequenced...
November 30, 2018: Science
Lehang Lin, Moli Huang, Xianping Shi, Anand Mayakonda, Kaishun Hu, Yan-Yi Jiang, Xiao Guo, Li Chen, Brendan Pang, Ngan Doan, Jonathan W Said, Jianjun Xie, Sigal Gery, Xu Cheng, Zhaoyu Lin, Jinsong Li, Benjamin P Berman, Dong Yin, De-Chen Lin, H Phillip Koeffler
As the second most common malignant bone tumor in children and adolescents, Ewing sarcoma is initiated and exacerbated by a chimeric oncoprotein, most commonly, EWS-FLI1. In this study, we apply epigenomic analysis to characterize the transcription dysregulation in this cancer, focusing on the investigation of super-enhancer and its associated transcriptional regulatory mechanisms. We demonstrate that super-enhancer-associated transcripts are significantly enriched in EWS-FLI1 target genes, contribute to the aberrant transcriptional network of the disease, and mediate the exceptional sensitivity of Ewing sarcoma to transcriptional inhibition...
November 28, 2018: Nucleic Acids Research
Zhong Guan, Haixin Yu, Katarina Cuk, Yan Zhang, Hermann Brenner
Whole-blood DNA methylation markers have been suggested as potential biomarkers for early detection of breast cancer (BC). We conducted a systematic review of literature on whole-blood DNA methylation markers for BC detection. PubMed and ISI Web of Knowledge were searched up to 29th May 2018. Overall, 33 studies evaluating 355 markers were included. The diagnostic value of most individual markers was relatively modest, with only 6 markers showing sensitivity >40% at specificity >75% (only 2 (HYAL2 and S100P) were independently validated)...
November 28, 2018: Cancer Epidemiology, Biomarkers & Prevention
Florencio Pazos, Adrian Garcia-Moreno, Juan C Oliveros
BACKGROUND: Epigenetic phenomena are crucial for explaining the phenotypic plasticity seen in the cells of different tissues, developmental stages and diseases, all holding the same DNA sequence. As technology is allowing to retrieve epigenetic information in a genome-wide fashion, massive epigenomic datasets are being accumulated in public repositories. New approaches are required to mine those data to extract useful knowledge. We present here an automatic approach for detecting genomic regions with epigenetic variation patterns across samples related to a grouping of these samples, as a way of detecting regions functionally associated to the phenomenon behind the classification...
November 28, 2018: BMC Genomics
Eniko Papp, Dorothy Hallberg, Gottfried E Konecny, Daniel C Bruhm, Vilmos Adleff, Michaël Noë, Ioannis Kagiampakis, Doreen Palsgrove, Dylan Conklin, Yasuto Kinose, James R White, Michael F Press, Ronny Drapkin, Hariharan Easwaran, Stephen B Baylin, Dennis Slamon, Victor E Velculescu, Robert B Scharpf
To improve our understanding of ovarian cancer, we performed genome-wide analyses of 45 ovarian cancer cell lines. Given the challenges of genomic analyses of tumors without matched normal samples, we developed approaches for detection of somatic sequence and structural changes and integrated these with epigenetic and expression alterations. Alterations not previously implicated in ovarian cancer included amplification or overexpression of ASXL1 and H3F3B, deletion or underexpression of CDC73 and TGF-beta receptor pathway members, and rearrangements of YAP1-MAML2 and IKZF2-ERBB4...
November 27, 2018: Cell Reports
Hirokazu Okayama, Masaru Noda, Koji Kono
No abstract text is available yet for this article.
November 2, 2018: Oncotarget
Camilla Restellini, Alessandro Cuomo, Michela Lupia, Marco Giordano, Tiziana Bonaldi, Roberta Noberini
PURPOSE: Profiling histone post-translational modifications (PTMs) in clinical samples holds great potential for the identification of epigenetic biomarkers and the discovery of novel epigenetic targets. Mass spectrometry (MS)-based approaches to analyze histone PTMs in clinical samples usually rely on SDS-PAGE separation following histone enrichment in order to eliminate detergents and further isolate histones. However, this limits the digestions options and hence the modification coverage...
November 24, 2018: Proteomics. Clinical Applications
Marc D Ryser, Ming Yu, William Grady, Kimberly Siegmund, Darryl Shibata
Genomic intratumoral heterogeneity (ITH) is common in cancers, but the extent of phenotypic ITH is uncertain because most subclonal mutations are passengers. Since tumor phenotypes are largely driven by epigenetics, methylomic analyses can provide insights into phenotypic ITH. Following this principle, we determined the extent of epigenetic ITH in 16 human colorectal tumors by comparing the methylomes from spatially separated regions in each tumor. Methylomes from opposite tumor sides were similar (Pearson correlation >0...
November 23, 2018: Scientific Reports
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