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https://www.readbyqxmd.com/read/28737768/arid1a-mutated-ovarian-cancers-depend-on-hdac6%C3%A2-activity
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28729426/glycerol-3-phosphate-acyltransferase-2-is-essential-for-normal-spermatogenesis
#16
Maria Belen Garcia-Fabiani, Mauro A Montanaro, Pablo Stringa, Ezequiel Lacunza, Elizabeth R Cattaneo, Marianela Santana, Magali Pellon-Maison, Maria R Gonzalez-Baro
Glycerol-3-phosphate acyltransferases (GPAT) catalyze the first and rate-limiting step in the de novo glycerolipid synthesis. The GPAT2 isoform differs from the other isoforms because its expression is restricted to male germ cells and cancer cells. It has been recently reported that GPAT2 expression in mouse testis fluctuates during sexual maturation and that it is regulated by epigenetic mechanisms in combination with vitamin A derivatives. Despite progress made in this field, information about GPAT2 role in the developing male germ cells remains unclear...
July 20, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28728135/prostate-cancer-risk-and-dna-methylation-signatures-in-aging-rats-following-developmental-bpa-exposure-a-dose-response-analysis
#17
Gail S Prins, Shu-Hua Ye, Lynn Birch, Xiang Zhang, Ana Cheong, Han Lin, Esther Calderon-Gierszal, Jacob Groen, Wen-Yang Hu, Shuk-Mei Ho, Richard B van Breemen
BACKGROUND: Previous studies have uncovered heightened prostatic susceptibility to hormone-induced neoplasia from early-life exposure to low-dose bisphenol A (BPA). However, significant data gaps remain that are essential to address for biological relevance and necessary risk assessment. OBJECTIVES: A complete BPA dose-response analysis of prostate lesions across multiple prostatic lobes was conducted that included internal BPA dosimetry, progression to adenocarcinoma with aging and mechanistic connections to epigenetically reprogramed genes...
July 11, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28726821/the-whole-genome-landscape-of-medulloblastoma-subtypes
#18
Paul A Northcott, Ivo Buchhalter, A Sorana Morrissy, Volker Hovestadt, Joachim Weischenfeldt, Tobias Ehrenberger, Susanne Gröbner, Maia Segura-Wang, Thomas Zichner, Vasilisa A Rudneva, Hans-Jörg Warnatz, Nikos Sidiropoulos, Aaron H Phillips, Steven Schumacher, Kortine Kleinheinz, Sebastian M Waszak, Serap Erkek, David T W Jones, Barbara C Worst, Marcel Kool, Marc Zapatka, Natalie Jäger, Lukas Chavez, Barbara Hutter, Matthias Bieg, Nagarajan Paramasivam, Michael Heinold, Zuguang Gu, Naveed Ishaque, Christina Jäger-Schmidt, Charles D Imbusch, Alke Jugold, Daniel Hübschmann, Thomas Risch, Vyacheslav Amstislavskiy, Francisco German Rodriguez Gonzalez, Ursula D Weber, Stephan Wolf, Giles W Robinson, Xin Zhou, Gang Wu, David Finkelstein, Yanling Liu, Florence M G Cavalli, Betty Luu, Vijay Ramaswamy, Xiaochong Wu, Jan Koster, Marina Ryzhova, Yoon-Jae Cho, Scott L Pomeroy, Christel Herold-Mende, Martin Schuhmann, Martin Ebinger, Linda M Liau, Jaume Mora, Roger E McLendon, Nada Jabado, Toshihiro Kumabe, Eric Chuah, Yussanne Ma, Richard A Moore, Andrew J Mungall, Karen L Mungall, Nina Thiessen, Kane Tse, Tina Wong, Steven J M Jones, Olaf Witt, Till Milde, Andreas Von Deimling, David Capper, Andrey Korshunov, Marie-Laure Yaspo, Richard Kriwacki, Amar Gajjar, Jinghui Zhang, Rameen Beroukhim, Ernest Fraenkel, Jan O Korbel, Benedikt Brors, Matthias Schlesner, Roland Eils, Marco A Marra, Stefan M Pfister, Michael D Taylor, Peter Lichter
Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28726739/5-aza-2-2-difluroro-deoxycytidine-nuc013-a-novel-nucleoside-dna-methyl-transferase-inhibitor-and-ribonucleotide-reductase-inhibitor-for-the-treatment-of-cancer
#19
Richard Daifuku, Zhenbo Hu, Yogen Saunthararajah
Tumor suppressor genes can be silenced genetically as well as epigenetically. One approach to reversing epigenetic suppression of tumor suppressor genes is to inhibit DNA methyl transferase. 5-aza-2',2'-diflurorodeoxycytidine (NUC013) is a novel DNA methyl transferase and ribonucleotide reductase inhibitor that is a more potent inhibitor of growth than decitabine in the NCI 60 cancer cell line panel. NUC013 is more active than decitabine against p53-null/mutant cancer cell lines (p = 0.027) but is even more so against p53 wild-type (WT) cell lines (p = 0...
July 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28725537/the-emerging-role-of-histone-demethylases-in-renal-cell-carcinoma
#20
REVIEW
Xiaoqiang Guo, Qiaoxia Zhang
Renal cell carcinoma (RCC), the most common kidney cancer, is responsible for more than 100,000 deaths per year worldwide. The molecular mechanism of RCC is poorly understood. Many studies have indicated that epigenetic changes such as DNA methylation, noncoding RNAs, and histone modifications are central to the pathogenesis of cancer. Histone demethylases (KDMs) play a central role in histone modifications. There is emerging evidence that KDMs such as KDM3A, KDM5C, KDM6A, and KDM6B play important roles in RCC...
2017: Journal of Kidney Cancer and VHL
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