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Cancer epigenomics

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https://www.readbyqxmd.com/read/29161273/enrichment-of-colorectal-cancer-associations-in-functional-regions-insight-for-using-epigenomics-data-in-the-analysis-of-whole-genome-sequence-imputed-gwas-data
#1
Stephanie A Bien, Paul L Auer, Tabitha A Harrison, Conghui Qu, Charles M Connolly, Peyton G Greenside, Sai Chen, Sonja I Berndt, Stéphane Bézieau, Hyun M Kang, Jeroen Huyghe, Hermann Brenner, Graham Casey, Andrew T Chan, John L Hopper, Barbara L Banbury, Jenny Chang-Claude, Stephen J Chanock, Robert W Haile, Michael Hoffmeister, Christian Fuchsberger, Mark A Jenkins, Suzanne M Leal, Mathieu Lemire, Polly A Newcomb, Steven Gallinger, John D Potter, Robert E Schoen, Martha L Slattery, Joshua D Smith, Loic Le Marchand, Emily White, Brent W Zanke, Goncalo R Abeçasis, Christopher S Carlson, Ulrike Peters, Deborah A Nickerson, Anshul Kundaje, Li Hsu
BACKGROUND: The evaluation of less frequent genetic variants and their effect on complex disease pose new challenges for genomic research. To investigate whether epigenetic data can be used to inform aggregate rare-variant association methods (RVAM), we assessed whether variants more significantly associated with colorectal cancer (CRC) were preferentially located in non-coding regulatory regions, and whether enrichment was specific to colorectal tissues. METHODS: Active regulatory elements (ARE) were mapped using data from 127 tissues and cell-types from NIH Roadmap Epigenomics and Encyclopedia of DNA Elements (ENCODE) projects...
2017: PloS One
https://www.readbyqxmd.com/read/29154989/targeting-bromodomain-and-extraterminal-proteins-in-breast-cancer
#2
REVIEW
Jennifer M Sahni, Ruth A Keri
Breast cancer is a collection of distinct tumor subtypes that are driven by unique gene expression profiles. These transcriptomes are controlled by various epigenetic marks that dictate which genes are expressed and suppressed. During carcinogenesis, extensive restructuring of the epigenome occurs, including aberrant acetylation, alteration of methylation patterns, and accumulation of epigenetic readers at oncogenes. As epigenetic alterations are reversible, epigenome-modulating drugs could provide a mechanism to silence numerous oncogenes simultaneously...
November 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29147491/augmented-expression-levels-of-lncrnas-eccebpa-and-uca1-in-gastric-cancer-tissues-and-their-clinical-significance
#3
Mojdeh Nasrollahzadeh-Khakiani, Modjtaba Emadi-Baygi, Parvaneh Nikpour
Objectives: As the second cause of cancer death, gastric cancer (GC) is one of the eminent dilemmas all over the world, therefore investigating the molecular mechanisms involved in this cancer is pivotal. Unrestricted proliferation is one of the characteristics of cancerous cells, which is due to deficiency in cell regulatory systems. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of the epigenome. lncRNA extra coding CEBPA (ecCEBPA) is involved in DNA methylation...
October 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29144447/bcat1-restricts-%C3%AE-kg-levels-in-aml-stem-cells-leading-to-idhmut-like-dna-hypermethylation
#4
Simon Raffel, Mattia Falcone, Niclas Kneisel, Jenny Hansson, Wei Wang, Christoph Lutz, Lars Bullinger, Gernot Poschet, Yannic Nonnenmacher, Andrea Barnert, Carsten Bahr, Petra Zeisberger, Adriana Przybylla, Markus Sohn, Martje Tönjes, Ayelet Erez, Lital Adler, Patrizia Jensen, Claudia Scholl, Stefan Fröhling, Sibylle Cocciardi, Patrick Wuchter, Christian Thiede, Anne Flörcken, Jörg Westermann, Gerhard Ehninger, Peter Lichter, Karsten Hiller, Rüdiger Hell, Carl Herrmann, Anthony D Ho, Jeroen Krijgsveld, Bernhard Radlwimmer, Andreas Trumpp
The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29137428/pten-loss-is-associated-with-prostate-cancer-recurrence-and-alterations-in-tumor-dna-methylation-profiles
#5
Milan S Geybels, Min Fang, Jonathan L Wright, Xiaoyu Qu, Marina Bibikova, Brandy Klotzle, Jian-Bing Fan, Ziding Feng, Elaine A Ostrander, Peter S Nelson, Janet L Stanford
Background: Prostate cancer (PCa) with loss of the tumor suppressor gene PTEN has an unfavorable prognosis. DNA methylation profiles associated with PTEN loss may provide further insights into the mechanisms underlying these more aggressive, clinically relevant tumors. Methods: The cohort included patients with clinically localized PCa. Samples taken from the primary tumor were used to determine PTEN genomic deletions using FISH, and to analyze epigenome-wide DNA methylation profiles...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29128106/who-are-the-long-term-survivors-of-high-grade-serous-ovarian-cancer
#6
REVIEW
Claire Hoppenot, Mark A Eckert, Samantha M Tienda, Ernst Lengyel
Although the median survival for epithelial ovarian cancer (EOC) is <5years, approximately 15% of patients will survive for >10years. A better understanding of these exceptional responders could reveal opportunities to improve the dismal prognosis of most EOC patients. In this review, we examine the clinical and genomic features that have been associated with long-term survival, which is generally defined as survival of >7-10years after initial diagnosis. Clinical features influencing long-term survival have been best reported in large retrospective population-based studies...
November 8, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29126224/dbtss-dbkero-for-integrated-analysis-of-transcriptional-regulation
#7
Ayako Suzuki, Shin Kawano, Toutai Mitsuyama, Mikita Suyama, Yae Kanai, Katsuhiko Shirahige, Hiroyuki Sasaki, Katsushi Tokunaga, Katsuya Tsuchihara, Sumio Sugano, Kenta Nakai, Yutaka Suzuki
DBTSS (Database of Transcriptional Start Sites)/DBKERO (Database of Kashiwa Encyclopedia for human genome mutations in Regulatory regions and their Omics contexts) is the database originally initiated with the information of transcriptional start sites and their upstream transcriptional regulatory regions. In recent years, we updated the database to assist users to elucidate biological relevance of the human genome variations or somatic mutations in cancers which may affect the transcriptional regulation. In this update, we facilitate interpretations of disease associated genomic variation, using the Japanese population as a model case...
November 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29125844/significant-associations-between-driver-gene-mutations-and-dna-methylation-alterations-across-many-cancer-types
#8
Yun-Ching Chen, Valer Gotea, Gennady Margolin, Laura Elnitski
Recent evidence shows that mutations in several driver genes can cause aberrant methylation patterns, a hallmark of cancer. In light of these findings, we hypothesized that the landscapes of tumor genomes and epigenomes are tightly interconnected. We measured this relationship using principal component analyses and methylation-mutation associations applied at the nucleotide level and with respect to genome-wide trends. We found that a few mutated driver genes were associated with genome-wide patterns of aberrant hypomethylation or CpG island hypermethylation in specific cancer types...
November 10, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29112206/intratumoral-heterogeneity-and-clonal-evolution-in-blood-malignancies-and-solid-tumors
#9
Ignacio Varela, Pablo Menendez, Alejandra Sanjuan-Pla
This meeting held at the University of Barcelona in March 2017, brought together scientists and clinicians worldwide to discuss current and future clinico-biological implications of intratumoral heterogeneity (ITH) and subclonal evolution in cancer diagnosis, patient stratification, and treatment resistance in diagnosis, treatment and follow-up. There was consensus that both longitudinal and tumor multi-region studies in matched samples are needed to better understand the dynamics of ITH. The contribution of the epigenome and microenvironment to ITH and subclone evolution remains understudied...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29111877/dna-methylation-alterations-induced-by-transient-exposure-of-mcf-7-cells-to-maghemite-nanoparticles
#10
Raphael S Bonadio, Ana Carolina Arcanjo, Emilia Cd Lima, Alline T Vasconcelos, Renata C Silva, Frederico H Horst, Ricardo B Azevedo, Marcio José Poças-Fonseca, João Paulo F Longo
AIM: To evaluate the DNA methylation profile of MCF-7 cells during and after the treatment with maghemite nanoparticles (MNP-CIT). MATERIALS & METHODS: Noncytotoxic MNP-CIT concentrations and cell morphology were evaluated by standard methods. DNA methylation was assessed by whole genome bisulfite sequencing. DNA methyltransferase (DNMT) genes expression was analyzed by qRT-PCR. RESULTS: A total of 30 and 60 µgFeml(-1) MNP-CIT accumulated in cytoplasm but did not present cytotoxic effects...
November 7, 2017: Nanomedicine
https://www.readbyqxmd.com/read/29111290/-transgenerational-impact-of-chemotherapy-would-the-father-exposure-impact-the-health-of-future-progeny
#11
A Tremblay, H Beaud, G Delbès
The number of cancer survivors is increasing and their quality of life is becoming a major public health issue. Cancer treatments reduce men's reproductive health by targeting spermatogenesis. Ultimately, DNA, chromatin and the epigenome of spermatozoa can be altered in cancer survivors. Knowing whether the history of cancer and the treatments received can have consequences on the health of their offspring is therefore a fundamental question for these patients. This review gathers the experimental and epidemiological evidences of the effects observed on the direct descendants and on several generations, and draws up the state of knowledge on the mechanisms potentially involved...
October 27, 2017: Gynecologie, Obstetrique, Fertilite & Senologie
https://www.readbyqxmd.com/read/29110627/the-impact-of-translational-research-in-breast-cancer-care-can-we-improve-the-therapeutic-scenario
#12
Francesco Perri, Giuseppe Buono, Francesco Schettini, Grazia Arpino, Roberto Bianco, Carmen Criscitiello, Sabino De Placido, Mario Giuliano
Traditionally, breast cancer (BC) is divided into different immunohistochemically (IHC)-defined subtypes, according to the expression of hormone receptors and overexpression/amplification of human epidermal growth factor receptor 2 (HER2), with crucial therapeutic implications. In the last few years, the definition of different BC molecular subgroups within the IHC-defined subtypes and the identification of the important role that molecular heterogeneity can play in tumor progression and treatment resistance have inspired the search for personalized therapeutic approaches...
November 2, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29109526/genome-wide-genetic-and-epigenetic-analyses-of-pancreatic-acinar-cell-carcinomas-reveal-aberrations-in-genome-stability
#13
Cornelia Jäkel, Frank Bergmann, Reka Toth, Yassen Assenov, Daniel van der Duin, Oliver Strobel, Thomas Hank, Günter Klöppel, Craig Dorrell, Markus Grompe, Joshua Moss, Yuval Dor, Peter Schirmacher, Christoph Plass, Odilia Popanda, Peter Schmezer
Pancreatic acinar cell carcinoma (ACC) is an aggressive exocrine tumor with largely unknown biology. Here, to identify potential targets for personalized treatment, we perform integrative genome-wide and epigenome-wide analyses. The results show frequently aberrant DNA methylation, abundant chromosomal amplifications and deletions, and mutational signatures suggesting defective DNA repair. In contrast to pancreatic ductal adenocarcinoma, no recurrent point mutations are detected. The tumor suppressors ID3, ARID1A, APC, and CDKN2A are frequently impaired also on the protein level and thus potentially affect ACC tumorigenesis...
November 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29107597/naked-mole-rat-cells-have-a-stable-epigenome-that-resists-ipsc%C3%A2-reprogramming
#14
Li Tan, Zhonghe Ke, Gregory Tombline, Nicholas Macoretta, Kevin Hayes, Xiao Tian, Ruitu Lv, Julia Ablaeva, Michael Gilbert, Natarajan V Bhanu, Zuo-Fei Yuan, Benjamin A Garcia, Yujiang G Shi, Yang Shi, Andrei Seluanov, Vera Gorbunova
Naked mole rat (NMR) is a valuable model for aging and cancer research due to its exceptional longevity and cancer resistance. We observed that the reprogramming efficiency of NMR fibroblasts in response to OSKM was drastically lower than that of mouse fibroblasts. Expression of SV40 LargeT antigen (LT) dramatically improved reprogramming of NMR fibroblasts. Inactivation of Rb alone, but not p53, was sufficient to improve reprogramming efficiency, suggesting that NMR chromatin may be refractory to reprogramming...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29102482/vitamin-c-a-new-player-in-regulation-of-the-cancer-epigenome
#15
REVIEW
Linn Gillberg, Andreas D Ørskov, Minmin Liu, Laurine B S Harsløf, Peter A Jones, Kirsten Grønbæk
Over the past few years it has become clear that vitamin C, as a provider of reduced iron, is an essential factor for the function of epigenetic regulators that initiate the demethylation of DNA and histones. Vitamin C deficiency is rare in the general population, but is frequently observed in patients with cancer. Genes encoding epigenetic regulators are often mutated in cancer, underscoring their central roles in carcinogenesis. In hematological cancers, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), drugs that reverse epigenetic aberrations are now the standard of care...
November 1, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29080966/adrenocortical-carcinoma-the-dawn-of-a-new-era-of-genomic-and-molecular-biology-analysis
#16
REVIEW
R Armignacco, G Cantini, L Canu, G Poli, T Ercolino, M Mannelli, M Luconi
Over the last decade, the development of novel and high penetrance genomic approaches to analyze biological samples has provided very new insights in the comprehension of the molecular biology and genetics of tumors. The use of these techniques, consisting of exome sequencing, transcriptome, miRNome, chromosome alteration, genome, and epigenome analysis, has also been successfully applied to adrenocortical carcinoma (ACC). In fact, the analysis of large cohorts of patients allowed the stratification of ACC with different patterns of molecular alterations, associated with different outcomes, thus providing a novel molecular classification of the malignancy to be associated with the classical pathological analysis...
October 28, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29080344/bile-acids-and-cancer-direct-and-environmental-dependent-effects
#17
Agostino Di Ciaula, David Q-H Wang, Emilio Molina-Molina, Raquel Lunardi Baccetto, Giuseppe Calamita, Vincenzo O Palmieri, Piero Portincasa
Bile acids (BAs) regulate the absorption of fat-soluble vitamins, cholesterol and lipids but have also a key role as singalling molecules and in the modulation of epithelial cell proliferation, gene expression and metabolism. These homeostatic pathways, when disrupted, are able to promote local inflammation, systemic metabolic disorders and, ultimately, cancer. The effect of hydrophobic BAs, in particular, can be linked with cancer in several digestive (mainly oesophagus, stomach, liver, pancreas, biliary tract, colon) and extra-digestive organs (i...
October 28, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/29079534/epigenetic-reprogramming-in-liver-fibrosis-and-cancer
#18
Caroline L Wilson, Derek A Mann, Lee A Borthwick
Novel insights into the epigenetic control of chronic liver diseases are now emerging. Recent advances in our understanding of the critical roles of DNA methylation, histone modifications and ncRNA may now be exploited to improve management of fibrosis/cirrhosis and cancer. Furthermore, improved technologies for the detection of epigenetic markers from patients' blood and tissues will vastly improve diagnosis, treatment options and prognostic tracking. The aim of this review is to present recent findings from the field of liver epigenetics and to explore their potential for translation into therapeutics to prevent disease promoting epigenome reprogramming and reverse epigenetic changes...
October 25, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29078205/intratumor-and-intertumor-heterogeneity-in-melanoma
#19
REVIEW
Tomasz M Grzywa, Wiktor Paskal, Paweł K Włodarski
Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment...
December 2017: Translational Oncology
https://www.readbyqxmd.com/read/29076965/mutational-and-epigenetic-signatures-in-cancer-tissue-linked-to-environmental-exposures-and-lifestyle
#20
Vittorio Perduca, Hanane Omichessan, Laura Baglietto, Gianluca Severi
PURPOSE OF REVIEW: In this article, we describe how recent advances in the study of mutational and epigenetic signatures in tumours provide new opportunities to understand the role of the environment and lifestyle in cancer development. RECENT FINDINGS: Cancer-related mutational events have been investigated for decades but only recently the wide availability of genomic sequences and epigenomic data from thousands of cancer genomes has made it possible to identify numerous distinct mutational and epigenetic signatures through the application of advanced mathematical models...
October 25, 2017: Current Opinion in Oncology
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