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Cancer epigenetics

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https://www.readbyqxmd.com/read/28742980/disease-relevant-modifications-of-the-methylome-and-transcriptome-by-particulate-matter-pm2-5-from-biomass-combustion
#1
Katharina Heßelbach, Gwang-Jin Kim, Stephan Flemming, Thomas Häupl, Marc Bonin, Regina Dornhof, Stefan Günther, Irmgard Merfort, Matjaz Humar
Exposure to particulate matter (PM) is recognized as a major health hazard, but molecular responses are still insufficiently described. We analyzed the epigenetic impact of ambient PM2.5 from biomass combustion on the methylome of primary human bronchial epithelial BEAS-2B cells using the Illumina HumanMethylation450 BeadChip. The transcriptome was determined by the Affymetrix HG-U133 Plus 2.0 Array. PM2.5 induced genome wide alterations of the DNA methylation pattern, including differentially methylated CpGs in the promoter region associated with CpG islands...
July 25, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28741490/in-vivo-rnai-screening-for-pancreatic-cancer-drivers-piloting-the-wdr5-myc-axis
#2
Günter Schneider, Dieter Saur
Pancreatic ductal adenocarcinoma (PDAC) represents a major global health problem that causes over 200000 deaths each year worldwide. The disease is highly resistant to cytotoxic and targeted therapies and the average survival is less than 12 months. This situation prompted Alessandro Carugo and Giulio Draetta to develop a novel genetic mouse system, termed Patient-Based In Vivo Lethality to Optimize Treatment (PILOT), to perform functional RNAi-based in vivo screens to uncover and target PDAC drivers. In a forward genetic screen focused on epigenetic modifiers, a WDR5-Myc axis that regulates the DNA replication checkpoint was identified and exploited in vivo for therapeutic intervention...
August 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28741488/extraordinary-cancer-epigenomics-thinking-outside-the-classical-coding-and-promoter-box
#3
REVIEW
Matthew Murtha, Manel Esteller
The advent of functional genomics powered by high-throughput sequencing has given us a new appreciation of the genomic sequences that lie outside the canonical promoter-coding sequence box. These regions harbor distant regulatory elements, enhancers, super-enhancers, insulators, alternative promoters, and sequences that transcribe as noncoding RNAs (ncRNAs) such as miRNAs and long ncRNAs. These functional genomics studies have also enabled a clearer understanding of the role of the 3D structure of the genome in epigenetic regulation...
October 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28740569/dna-oncogenic-virus-induced-oxidative-stress-genomic-damage-and-aberrant-epigenetic-alterations
#4
REVIEW
Mankgopo Magdeline Kgatle, Catherine Wendy Spearman, Asgar Ali Kalla, Henry Norman Hairwadzi
Approximately 20% of human cancers is attributable to DNA oncogenic viruses such as human papillomavirus (HPV), hepatitis B virus (HBV), and Epstein-Barr virus (EBV). Unrepaired DNA damage is the most common and overlapping feature of these DNA oncogenic viruses and a source of genomic instability and tumour development. Sustained DNA damage results from unceasing production of reactive oxygen species and activation of inflammasome cascades that trigger genomic changes and increased propensity of epigenetic alterations...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28738804/oncogenic-long-noncoding-rna-landscape-in-breast-cancer
#5
Shouping Xu, Dejia Kong, Qianlin Chen, Yanyan Ping, Da Pang
BACKGROUND: Few long noncoding RNAs (lncRNAs) that act as oncogenic genes in breast cancer have been identified. METHODS: Oncogenic lncRNAs associated with tumourigenesis and worse survival outcomes were examined and validated in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), respectively. Then, the potential biological functions and expression regulation of these lncRNAs were studied via bioinformatics and genome data analysis. Moreover, progressive breast cancer subtype-specific lncRNAs were investigated via high-throughput sequencing in our cohort and TCGA validation...
July 24, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28737768/arid1a-mutated-ovarian-cancers-depend-on-hdac6%C3%A2-activity
#6
Benjamin G Bitler, Shuai Wu, Pyoung Hwa Park, Yang Hai, Katherine M Aird, Yemin Wang, Yali Zhai, Andrew V Kossenkov, Ana Vara-Ailor, Frank J Rauscher Iii, Weiping Zou, David W Speicher, David G Huntsman, Jose R Conejo-Garcia, Kathleen R Cho, David W Christianson, Rugang Zhang
ARID1A, encoding a subunit of the SWI/SNF chromatin-remodelling complex, is the most frequently mutated epigenetic regulator across all human cancers. ARID1A and TP53 mutations are typically mutually exclusive. Therapeutic approaches that correlate with this genetic characteristic remain to be explored. Here, we show that HDAC6 activity is essential in ARID1A-mutated ovarian cancers. Inhibition of HDAC6 activity using a clinically applicable small-molecule inhibitor significantly improved the survival of mice bearing ARID1A-mutated tumours...
July 24, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28737694/the-role-of-p16-ink4a-pathway-in-human-epidermal-stem-cell-self-renewal-aging-and-cancer
#7
REVIEW
Daniela D'Arcangelo, Lavinia Tinaburri, Elena Dellambra
The epidermis is a self-renewing tissue. The balance between proliferation and differentiation processes is tightly regulated to ensure the maintenance of the stem cell (SC) population in the epidermis during life. Aging and cancer may be considered related endpoints of accumulating damages within epidermal self-renewing compartment. p16(INK4a) is a potent inhibitor of the G1/S-phase transition of the cell cycle. p16(INK4a) governs the processes of SC self-renewal in several tissues and its deregulation may result in aging or tumor development...
July 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28736730/new-insight-into-microrna-functions-in-cancer-oncogene-microrna-tumor-suppressor-gene-network
#8
REVIEW
Kecheng Zhou, Minxia Liu, Yi Cao
Tumorigenesis is a multi-step and complex process with multi-factors involved. Deregulated oncogenes and tumor suppressor genes (TSGs) induced by genetic and epigenetic factors are considered as the driving force in the development and progression of cancer. Besides, microRNAs (miRNAs) act vital roles in tumorigenesis through regulating some oncogenes and TSGs. Interestingly, miRNAs are also regulated by oncogenes and TSGs. Considering the entangled regulation, here we propose a new insight into these regulation relationships in cancer: oncogene-miRNA-TSG network, which further emphasizes roles of miRNA, as well as highlights the network regulation among oncogene, miRNA, and TSG during tumorigenesis...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28736626/molecular-landscape-and-sub-classification-of-gastrointestinal-cancers-a-review-of-literature
#9
REVIEW
Bita Fakhri, Kian-Huat Lim
The historical approach of diagnosing cancer types based entirely on anatomic origin and histologic features, and the "one-size-fit-all" therapeutic approach, are inadequate in modern cancer treatment. From decades of research we now know that cancer is a highly heterogeneous disease driven by complex genetic or epigenetic alterations. The advent of various high throughput molecular tools has now enabled us to view and sub-classify each cancer type based on their distinct molecular features, in addition to histologic classification, with the promise of individualized treatment strategies tailored towards each specific subtype to improve patient outcomes...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28735685/utilizing-circulating-tumour-dna-in-radiation-oncology
#10
REVIEW
Ariana Rostami, Scott V Bratman
Emerging technologies for detection of circulating tumour DNA (ctDNA) are expanding the possibilities for clinical impact to patients with localized, potentially curable cancer. For such patients, ctDNA analysis could aid in prognostication, prediction of treatment response, longitudinal monitoring for adaptive treatment, and evaluation of minimal residual disease. Radiation oncologists currently have few tools at their disposal for predicting or rapidly assessing treatment efficacy. By reflecting the genetic and epigenetic makeup of tumours as well as dynamic changes with treatment, ctDNA as a biomarker for radiation response could enable new personalized treatment approaches...
July 20, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28735485/genome-wide-analysis-of-dna-methylation-in-hematopoietic-cells-dna-methylation-analysis-by-wgbs
#11
Mira Jeong, Anna G Guzman, Margaret A Goodell
DNA methylation is a major epigenetic modification that regulates gene expression, genome imprinting, and development and has a role in diseases including cancer. There are various methods for whole-genome methylation profiling that differ in cost and resolution. Recent advances in high-throughput sequencing technologies coupled with bisulfite treatment enable absolute DNA methylation quantification and genome-wide single-nucleotide resolution analysis. In this chapter, we provide detailed protocols for whole-genome bisulfite sequencing (WGBS), which captures the complete methylome...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28735484/microsphere-based-assessment-of-dna-methylation-for-aml-prognosis
#12
Gerald B W Wertheim, Marlise R Luskin, Martin Carroll, Stephen R Master
Epigenetic dysregulation, including aberrant methylation of cytosine residues in DNA, is a hallmark of cancer and clearly results in oncogenic cellular alterations such as transcriptional attenuation of tumor suppressors and genomic instability. A number of studies have examined DNA methylation alterations in patients with acute myeloid leukemia (AML) and have shown that analysis of multilocus methylation patterns can identify biologically distinct AML subclasses and can predict patient prognosis. In order to utilize the prognostic capability of methylation analysis in a clinical setting, we have developed a microsphere-based HpaII tiny fragment enrichment by ligation-mediated PCR (xMELP) assay to interrogate the methylation state of genomic multiple loci along with a random forest-based classification algorithm that correlates DNA methylation status with patient prognosis...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28734980/histone-demethylase-phf8-regulates-hypoxia-signaling-through-hif1%C3%AE-and-h3k4me3
#13
Peterson Kariuki Maina, Peng Shao, Xiongfei Jia, Qi Liu, Shaikamjad Umesalma, Maximo Marin, Donald Long, Samantha Concepción-Román, Hank Heng Qi
Hypoxia through transcription factor HIF1α plays a critical role in cancer development. In prostate cancer, HIF1α interplays with androgen receptor (AR) to contribute to the progression of this disease to its lethal form-castration-resistant prostate cancer (CRPC). Hypoxia upregulates several epigenetic factors including histone demethylase KDM3A which is a critical co-factor of HIF1α. However, how histone demethylases regulate hypoxia signaling is not fully understood. Here, we report that histone demethylase PHF8 plays an essential role in hypoxia signaling...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28734945/the-epigenomic-revolution-in-breast-cancer-from-single-gene-to-genome-wide-next-generation-approaches
#14
REVIEW
Veronica Davalos, Anna Martinez-Cardus, Manel Esteller
From the first identification of aberrant DNA methylation in primary human tumors more than three decades ago, exponential progress in cancer epigenetics research has been made. For many years, cancer epigenetics studies relied on identification of DNA methylation and histone modifications at specific genes. These studies laid the foundation for the field and revealed the epigenetic alterations as hallmark of cancer, as well as the crucial role of epigenetic mechanisms in tumorigenesis. The introduction of next-generation sequencing and array-based technologies for analyzing epigenetic states has accelerated our understanding about cancer and nowadays have become potent tools in our fight against the disease...
July 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28733542/use-of-a-genome-wide-haploid-genetic-screen-to-identify-treatment-predicting-factors-a-proof-of-principle-study-in-pancreatic-cancer
#15
Yuk Ting Ma, Sarah M Leonard, Naheema Gordon, Jennifer Anderton, Claire James, David Huen, Ciaran B Woodman, Daniel H Palmer
The ability to develop a comprehensive panel of treatment predicting factors would significantly improve our ability to stratify patients for cytotoxic or targeted therapies, and prevent patients receiving ineffective treatments. We have investigated if a recently developed genome-wide haploid genetic screen can be used to reveal the critical mediators of response to anticancer therapy. Pancreatic cancer is known to be highly resistant to systemic therapy. Recently epigenetic changes have been shown to be a key determinant in the maintenance of subpopulations of cancer cells with high-level resistance to cytotoxic therapy...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732378/acetylation-and-deacetylation-in-cancer-stem-like-cells
#16
REVIEW
Na Liu, Shiqi Li, Nan Wu, Kin-Sang Cho
Cancer stem-like cell (CSC) model has been established to investigate the underlying mechanisms of tumor initiation and progression. The imbalance between acetylation and deacetylation of histone or non-histone proteins, one of the important epigenetic modification processes, is closely associated with a wide variety of diseases including cancer. Acetylation and deacetylation are involved in various stemness-related signal pathways and drive the regulation of self-renewal and differentiation in normal developmental processes...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732347/histone-demethylase-jmjd2c-epigenetic-regulators-in-tumors
#17
REVIEW
Chengcheng Zhang, Zhongqi Wang, Qing Ji, Qi Li
Histone methylation is one of the major epigenetic modifications, and various histone methylases and demethylases participate in the epigenetic regulating. JMJD2C has been recently identified as one of the histone lysine demethylases. As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28730333/identification-of-a-novel-leukemic-specific-splice-variant-of-dnmt3b-and-its-stability
#18
Prachi Singh, Sarvagalla Sailu, Elango Palchamy, Mohane Selvaraj Coumar, Sudhakar Baluchamy
DNA methyltransferases make use of alternative splicing mechanism to generate various splice variants, but their role(s) in modulating DNA methylation patterns in the cells is unclear. Notably, DNMT3B alone contains nearly 40 different splice variants. In this study, we have identified a novel splice variant of DNMT3B, which lacks exon 7 and 10 from leukemic cell lines which we termed as DNMT3B9. The exon 7 codes for the major part of PWWP domain, and exon 10 inclusion serves as a pluripotent marker. By quantitative RT-PCR using exon-exon junction-specific primers, we showed higher level of DNMT3B9 transcripts in several leukemic cell lines...
August 2017: Medical Oncology
https://www.readbyqxmd.com/read/28730284/a-novel-interplay-between-hotair-and-dna-methylation-in-osteosarcoma-cells-indicates-a-new-therapeutic-strategy
#19
Xingang Li, Hongming Lu, Guilian Fan, Miao He, Yu Sun, Kai Xu, Fengjun Shi
PURPOSE: Osteosarcoma (OS) is one of the most prevalent primary malignant bone tumors in adolescent. HOTAIR is highly expressed and associated with the epigenetic modifications, especially DNA methylation, in cancer. However, the regulation mechanism between HOTAIR and DNA methylation and the biological effects of them in the pathogenesis of osteosarcoma remains elusive. METHOD: Through RNA-sequencing and computational analysis, followed by a variety of experimental validations, we report a novel interplay between HOTAIR, miR-126, and DNA methylation in OS...
July 20, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28729483/epigenetic-plasticity-and-the-hallmarks-of-cancer
#20
REVIEW
William A Flavahan, Elizabeth Gaskell, Bradley E Bernstein
Chromatin and associated epigenetic mechanisms stabilize gene expression and cellular states while also facilitating appropriate responses to developmental or environmental cues. Genetic, environmental, or metabolic insults can induce overly restrictive or overly permissive epigenetic landscapes that contribute to pathogenesis of cancer and other diseases. Restrictive chromatin states may prevent appropriate induction of tumor suppressor programs or block differentiation. By contrast, permissive or "plastic" states may allow stochastic oncogene activation or nonphysiologic cell fate transitions...
July 21, 2017: Science
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