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https://www.readbyqxmd.com/read/28734945/the-epigenomic-revolution-in-breast-cancer-from-single-gene-to-genome-wide-next-generation-approaches
#1
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/28732347/histone-demethylase-jmjd2c-epigenetic-regulators-in-tumors
#2
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/28723630/functional-role-of-setd2-bap1-parp-3-and-pbrm1-candidate-genes-on-the-regulation-of-htert-gene-expression
#3
Hannah Linne, Hemad Yasaei, Alison Marriott, Amanda Harvey, Kefah Mokbel, Robert Newbold, Terry Roberts
Narrowing the search for the critical hTERT repressor sequence(s) has identified three regions on chromosome 3p (3p12-p21.1, 3p21.2 and 3p21.3-p22). However, the precise location and identity of the sequence(s) responsible for hTERT transcriptional repression remains elusive. In order to identify critical hTERT repressor sequences located within human chromosome 3p12-p22, we investigated hTERT transcriptional activity within 21NT microcell hybrid clones containing chromosome 3 fragments. Mapping of chromosome 3 structure in a single hTERT-repressed 21NT-#3fragment hybrid clone, revealed a 490kb region of deletion localised to 3p21...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722143/breast-cancer-stem-cells-as-last-soldiers-eluding-therapeutic-burn-a-hard-nut-to-crack
#4
REVIEW
Pritish Nilendu, Ajay Kumar, Azad Kumar, Jayanta K Pal, Nilesh Kumar Sharma
Cancer stem cells (CSCs) are found in many cancer types, including breast carcinoma. Breast cancer stem cells (BCSCs) are considered as seed of cancer formation and they are associated with metastasis and genotoxic drug resistance. Several studies highlighted the presence of BCSCs in tumor microenvironment and they are accentuated with several carcinoma events including metastasis and resistance to genotoxic drugs and they also rebound after genotoxic burn. Stemness properties of a small population of cells in carcinoma have provided clues regarding the role of tumor microenvironment in tumor pathophysiology...
July 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28718331/entinostat-for-the-treatment-of-breast-cancer
#5
Dario Trapani, Angela Esposito, Carmen Criscitiello, Luca Mazzarella, Marzia Locatelli, Ida Minchella, Saverio Minucci, Giuseppe Curigliano
Breast cancer accounts for 29% of malignant tumors. It is an heterogenous disease covering a spectrum of different molecular subtypes. Epigenetic aberrations may affect gene expression through DNA and histone proteins modifications thus promoting tumor progression and resistance to anti- tumor treatment. Area covered: This article explores the potential role of entinostat in the treatment of breast cancer. The clinical trials evaluating entinostat are discussed, highlighting preclinical data and early-phase clinical studies results...
July 24, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28708432/epigenetic-changes-of-the-esr1-gene-in-breast-tissue-of-healthy-women-a-missing-link-with-breast-cancer-risk-factors
#6
Abdolreza Daraei, Pantea Izadi, Ghasemali Khorasani, Nahid Nafissi, Mohammad Mehdi Naghizadeh, Nasim Younosi, Alipasha Meysamie, Yaser Mansoori, Milad Bastami, Javad Tavakkoly-Bazzaz
BACKGROUND: Reproductive history and obesity are among the well-recognized risk factors in the development of breast cancer, which are partially mediated by the increased exposure of breast tissues to estrogens. However, only a few studies have investigated the link between these risk factors and the pattern of methylation signatures in the breast tissue of healthy women. The role of estrogen receptor 1 (ESR1) gene hypermethylation is reportedly important in the development of breast cancer...
July 14, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28706132/identification-of-a-novel-metastasis-inducing-lncrna-which-suppresses-the-kai1-cd82-metastasis-suppressor-gene-and-is-upregulated-in-triple-negative-breast-cancer
#7
Ronni Aram, Iris Dotan, Agnes Hotz-Wagenblatt, Dan Canaani
Inactivation of tumor/metastasis suppressor genes via epigenetic silencing is a frequent event in human cancers. KAI1/CD82 is a metastasis suppressor gene whose normal protecting activity is deficient in twelve different solid malignancies. Here we have identified and characterized a primarily nuclear non-polyadenylated, antisense (as)-lncRNA, initiating upstream of the KAI1 human metastasis suppressor gene transcription start site; and elongating in the opposite direction to KAI1 mRNA. We show that the KAI1 promoter is bi-directional giving rise to KAI1 mRNA and its as-lncRNA...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28702092/pat-h-ms-coupled-with-laser-microdissection-to-study-histone-post-translational-modifications-in-selected-cell-populations-from-pathology-samples
#8
Roberta Noberini, Rémi Longuespée, Cristina Richichi, Giancarlo Pruneri, Mark Kriegsmann, Giuliana Pelicci, Tiziana Bonaldi
BACKGROUND: Aberrations in histone post-translational modifications (hPTMs) have been linked with various pathologies, including cancer, and could not only represent useful biomarkers but also suggest possible targetable epigenetic mechanisms. We have recently developed an approach, termed pathology tissue analysis of histones by mass spectrometry (PAT-H-MS), that allows performing a comprehensive and quantitative analysis of histone PTMs from formalin-fixed paraffin-embedded pathology samples...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28698407/ccctc-binding-factor-inhibits-breast-cancer-cell-proliferation-and-metastasis-via-inactivation-of-the-nuclear-factor-kappab-pathway
#9
Jie Wu, Peng-Chang Li, Jun-Yi Pang, Guo-You Liu, Xue-Min Xie, Jia-Yao Li, Yi-Cong Yin, Jian-Hua Han, Xiu-Zhi Guo, Ling Qiu
CCCTC-binding factor (CTCF) is an important epigenetic regulator implicated in multiple cellular processes, including growth, proliferation, differentiation, and apoptosis. Although CTCF deletion or mutation has been associated with human breast cancer, the role of CTCF in breast cancer is questionable. We investigated the biological functions of CTCF in breast cancer and the underlying mechanism. The results showed that CTCF expression in human breast cancer cells and tissues was significantly lower than that in normal breast cells and tissues...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28693600/normal-breast-tissue-dna-methylation-differences-at-regulatory-elements-are-associated-with-the-cancer-risk-factor-age
#10
Kevin C Johnson, E Andres Houseman, Jessica E King, Brock C Christensen
BACKGROUND: The underlying biological mechanisms through which epidemiologically defined breast cancer risk factors contribute to disease risk remain poorly understood. Identification of the molecular changes associated with cancer risk factors in normal tissues may aid in determining the earliest events of carcinogenesis and informing cancer prevention strategies. METHODS: Here we investigated the impact cancer risk factors have on the normal breast epigenome by analyzing DNA methylation genome-wide (Infinium 450 K array) in cancer-free women from the Susan G...
July 10, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28693231/impact-of-rassf1a-gene-methylation-on-the-metastatic-axillary-nodal-status-in-breast-cancer-patients
#11
Eva Jezkova, Pavol Zubor, Karol Kajo, Marian Grendar, Karol Dokus, Marian Adamkov, Zora Lasabova, Lukas Plank, Jan Danko
Hypermethylation of CpG islands is a hallmark of cancer and occurs at an early stage in breast tumorigenesis. To gain insight into the epigenetic switches that may promote and/or contribute to the initial neoplastic events during breast carcinogenesis, the present study focused on the DNA methylation profile of invasive breast carcinoma. The aim of the study was to evaluate the prognostic significance of Ras association domain family 1 isoform A (RASSF1A) promoter methylation status in operable breast cancer, and to analyze the utility of this biomarker regarding its association with metastatic and nonmetastatic axillary nodal status...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28691938/genetic-versus-epigenetic-brca1-silencing-pathways-clinical-effects-in-primary-ovarian-cancer-patients-a-study-of-the-tumor-bank-ovarian-cancer-consortium
#12
Tingting Sun, Ilary Ruscito, Desislava Dimitrova, Radoslav Chekerov, Hagen Kulbe, Udo Baron, Véronique Blanchard, Pierluigi Benedetti Panici, Silvia Darb-Esfahani, Jalid Sehouli, Sven Olek, Elena Ioana Braicu
OBJECTIVES: The aim of the present study was to assess in a large cohort of primary epithelial ovarian cancer patients the incidence and the clinical effect of BRCA1 genetic and epigenetic silencing mechanisms. METHODS: A total of 188 primary epithelial ovarian cancer patients, treated between 2000 and 2011 at the Charité University Hospital of Berlin, were included. The patients' tumor and blood samples were obtained from the Tumor Bank Ovarian Cancer Network (www...
July 6, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28690657/epigenetic-silencing-of-mort-is-an-early-event-in-cancer-and-is-associated-with-luminal-receptor-positive-breast-tumor-subtypes
#13
Lukas Vrba, Bernard Walter Futscher
Immortality is an essential characteristic of cancer cells; a recent transcriptomic study of epithelial cell immortalization has linked epigenetic silencing of the long noncoding RNA Mortal Obligate RNA Transcript (MORT; alias ZNF667-AS1) to this process. This study evaluated the epigenetic and transcriptional state of MORT in two premalignant conditions-ductal carcinomas in situ and colon adenomas. Results show that MORT silencing is an early epigenetic event in human carcinogenesis, likely occurring near the point where premalignant cells gain immortality; this epigenetic silencing is maintained throughout malignant transformation and metastatic growth...
June 2017: Journal of Breast Cancer
https://www.readbyqxmd.com/read/28682785/artificial-light-at-night-a-novel-lifestyle-risk-factor-for-metabolic-disorder-and-cancer-morbidity
#14
REVIEW
Abed E Zubidat, Abraham Haim
Both obesity and breast cancer are already recognized worldwide as the most common syndromes in our modern society. Currently, there is accumulating evidence from epidemiological and experimental studies suggesting that these syndromes are closely associated with circadian disruption. It has been suggested that melatonin (MLT) and the circadian clock genes both play an important role in the development of these syndromes. However, we still poorly understand the molecular mechanism underlying the association between circadian disruption and the modern health syndromes...
July 26, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28679371/cpg-promoter-methylation-of-the-alkbh3-alkylation-repair-gene-in-breast-cancer
#15
Olafur Andri Stefansson, Stefan Hermanowicz, Jasper van der Horst, Holmfridur Hilmarsdottir, Zuzanna Staszczak, Jon Gunnlaugur Jonasson, Laufey Tryggvadottir, Thorkell Gudjonsson, Stefan Sigurdsson
BACKGROUND: DNA repair of alkylation damage is defective in various cancers. This occurs through somatically acquired inactivation of the MGMT gene in various cancer types, including breast cancers. In addition to MGMT, the two E. coli AlkB homologs ALKBH2 and ALKBH3 have also been linked to direct reversal of alkylation damage. However, it is currently unknown whether ALKBH2 or ALKBH3 are found inactivated in cancer. METHODS: Methylome datasets (GSE52865, GSE20713, GSE69914), available through Omnibus, were used to determine whether ALKBH2 or ALKBH3 are found inactivated by CpG promoter methylation...
July 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28673967/piperlongumine-induces-reactive-oxygen-species-ros-dependent-downregulation-of-specificity-protein-transcription-factors
#16
Keshav Karki, Erik Hedrick, Ravi Kasiappan, Un-Ho Jin, Stephen Safe
Piperlongumine is a natural product found in the plant species Piper longum, and this compound exhibits potent anticancer activity in multiple tumor types and has been characterized as an inducer of reactive oxygen species (ROS). Treatment of Panc1 and L3.6pL pancreatic, A549 lung, 786-O kidney, and SKBR3 breast cancer cell lines with 5 to 15 μmol/L piperlongumine inhibited cell proliferation and induced apoptosis and ROS, and these responses were attenuated after cotreatment with the antioxidant glutathione...
July 3, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28659184/rerg-suppresses-cell-proliferation-migration-and-angiogenesis-through-erk-nf-%C3%AE%C2%BAb-signaling-pathway-in-nasopharyngeal-carcinoma
#17
Weilin Zhao, Ning Ma, Shumin Wang, Yingxi Mo, Zhe Zhang, Guangwu Huang, Kaoru Midorikawa, Yusuke Hiraku, Shinji Oikawa, Mariko Murata, Kazuhiko Takeuchi
BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignancy of the head and neck that is prevalent in Southeast Asia and southern China. Recent studies in epigenetics suggest that DNA methylation plays a pivotal role in the onset and progression of cancer. Combining the methyl-DNA binding domain capture technique and cDNA microarray analysis, we identified a unique hypermethylated gene, RERG (Ras-like estrogen-regulated growth inhibitor), that was down-regulated in NPC tissues. RERG is a tumor suppressor gene that was first reported in breast cancer...
June 28, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28657607/gut-microbiota-as-a-target-for-preventive-and-therapeutic-intervention-against-food-allergy
#18
REVIEW
Rosita Aitoro, Lorella Paparo, Antonio Amoroso, Margherita Di Costanzo, Linda Cosenza, Viviana Granata, Carmen Di Scala, Rita Nocerino, Giovanna Trinchese, Mariangela Montella, Danilo Ercolini, Roberto Berni Canani
The gut microbiota plays a pivotal role in immune system development and function. Modification in the gut microbiota composition (dysbiosis) early in life is a critical factor affecting the development of food allergy. Many environmental factors including caesarean delivery, lack of breast milk, drugs, antiseptic agents, and a low-fiber/high-fat diet can induce gut microbiota dysbiosis, and have been associated with the occurrence of food allergy. New technologies and experimental tools have provided information regarding the importance of select bacteria on immune tolerance mechanisms...
June 28, 2017: Nutrients
https://www.readbyqxmd.com/read/28649654/cell-state-plasticity-stem-cells-emt-and-the-generation-of-intra-tumoral-heterogeneity
#19
Geoffrey M Wahl, Benjamin T Spike
Cellular heterogeneity in cancer represents a significant challenge. In order to develop effective and lasting therapies, it is essential to understand the source of this heterogeneity, and its role in tumor progression and therapy resistance. Here, we consider not only genetic and epigenetic mechanisms, but also inflammation and cell state reprogramming in creating tumor heterogeneity. We discuss similarities between normal mammary epithelial developmental states and various breast cancer molecular sub-types, and the cells that are thought to propagate them...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28645612/il-1%C3%AE-induced-methylation-of-the-estrogen-receptor-er%C3%AE-gene-correlates-with-emt-and-chemoresistance-in-breast-cancer-cells
#20
Aura M Jiménez-Garduño, Mónica G Mendoza-Rodríguez, Daniel Urrutia-Cabrera, María C Domínguez-Robles, Eloy A Pérez-Yépez, Jorge Tonatiuh Ayala-Sumuano, Isaura Meza
Inflammation has been recently acknowledged as a key participant in the physiopathology of oncogenesis and tumor progression. The inflammatory cytokine IL-1β has been reported to induce the expression of markers associated with malignancy in breast cancerous cells through Epithelial-Mesenchymal Transition (EMT). Aggressive breast cancer tumors classified as Triple Negative do not respond to hormonal treatment because they lack three crucial receptors, one of which is the estrogen receptor alpha (ERα). Expression of ERα is then considered a good prognostic marker for tamoxifen treatment of this type of cancer, as the binding of this drug to the receptor blocks the transcriptional activity of the latter...
June 20, 2017: Biochemical and Biophysical Research Communications
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