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Cancer AND epigenom

Yi Ching Esther Wan, Jiaxian Liu, Kui Ming Chan
Histone modifications are one form of epigenetic information that relate closely to gene regulation. Aberrant histone methylation caused by alteration in chromatin-modifying enzymes has long been implicated in cancers. More recently, recurrent histone mutations have been identified in multiple cancers and have been shown to impede histone methylation. All three histone mutations (H3K27M, H3K36M, and H3G34V/R) identified result in amino acid substitution at/near a lysine residue that is a target of methylation...
2018: Current Pharmacology Reports
Michäel Duruisseaux, Anna Martínez-Cardús, Maria E Calleja-Cervantes, Sebastian Moran, Manuel Castro de Moura, Veronica Davalos, David Piñeyro, Montse Sanchez-Cespedes, Nicolas Girard, Marie Brevet, Etienne Giroux-Leprieur, Coraline Dumenil, Monica Pradotto, Paolo Bironzo, Enrica Capelletto, Silvia Novello, Alexis Cortot, Marie-Christine Copin, Niki Karachaliou, Maria Gonzalez-Cao, Sergio Peralta, Luis M Montuenga, Ignacio Gil-Bazo, Iosune Baraibar, Maria D Lozano, Mar Varela, Jose C Ruffinelli, Ramon Palmero, Ernest Nadal, Teresa Moran, Lidia Perez, Immaculada Ramos, Qingyang Xiao, Agustin F Fernandez, Mario F Fraga, Marta Gut, Ivo Gut, Cristina Teixidó, Noelia Vilariño, Aleix Prat, Noemi Reguart, Amparo Benito, Pilar Garrido, Isabel Barragan, Jean-François Emile, Rafael Rosell, Elisabeth Brambilla, Manel Esteller
BACKGROUND: Anti-programmed death-1 (PD-1) treatment for advanced non-small-cell lung cancer (NSCLC) has improved the survival of patients. However, a substantial percentage of patients do not respond to this treatment. We examined the use of DNA methylation profiles to determine the efficacy of anti-PD-1 treatment in patients recruited with current stage IV NSCLC. METHODS: In this multicentre study, we recruited adult patients from 15 hospitals in France, Spain, and Italy who had histologically proven stage IV NSCLC and had been exposed to PD-1 blockade during the course of the disease...
August 9, 2018: Lancet Respiratory Medicine
Byungjin Hwang, Ji Hyun Lee, Duhee Bang
Rapid progress in the development of next-generation sequencing (NGS) technologies in recent years has provided many valuable insights into complex biological systems, ranging from cancer genomics to diverse microbial communities. NGS-based technologies for genomics, transcriptomics, and epigenomics are now increasingly focused on the characterization of individual cells. These single-cell analyses will allow researchers to uncover new and potentially unexpected biological discoveries relative to traditional profiling methods that assess bulk populations...
August 7, 2018: Experimental & Molecular Medicine
Sarah J Aitken, Ximena Ibarra-Soria, Elissavet Kentepozidou, Paul Flicek, Christine Feig, John C Marioni, Duncan T Odom
BACKGROUND: CTCF binding to DNA helps partition the mammalian genome into discrete structural and regulatory domains. Complete removal of CTCF from mammalian cells causes catastrophic genome dysregulation, likely due to widespread collapse of 3D chromatin looping and alterations to inter- and intra-TAD interactions within the nucleus. In contrast, Ctcf hemizygous mice with lifelong reduction of CTCF expression are viable, albeit with increased cancer incidence. Here, we exploit chronic Ctcf hemizygosity to reveal its homeostatic roles in maintaining genome function and integrity...
August 7, 2018: Genome Biology
Xu Liang, Sophie Vacher, Anais Boulai, Virginie Bernard, Sylvain Baulande, Mylene Bohec, Ivan Bièche, Florence Lerebours, Céline Callens
BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive form of primary breast cancer. Using a custom-made breast cancer gene sequencing panel, we investigated somatic mutations in IBC to better understand the genomic differences compared with non-IBC and to consider new targeted therapy in IBC patients. METHODS: Targeted next-generation sequencing (NGS) of 91 candidate breast cancer-associated genes was performed on 156 fresh-frozen breast tumor tissues from IBC patients...
August 7, 2018: Breast Cancer Research: BCR
Matthew P Salomon, Xiaowen Wang, Diego M Marzese, Sandy C Hsu, Nellie Nelson, Xin Zhang, Chikako Matsuba, Yuki Takasumi, Carmen Ballesteros-Merino, Bernard A Fox, Garni Barkhoudarian, Daniel F Kelly, Dave S B Hoon
Purpose: Pituitary adenomas are one of the most common benign neoplasms of the central nervous system. Although emerging evidence suggests roles for both genetic and epigenetic factors in tumorigenesis, the degree to which these factors contribute to disease remains poorly understood. Experimental Design: A multiplatform analysis was performed to identify the genomic and epigenomic underpinnings of disease among the three major subtypes of surgically resected pituitary adenomas in 48 patients: growth hormone (GH)-secreting ( n = 17), adrenocorticotropic hormone (ACTH)-secreting ( n = 13, including 3 silent-ACTH adenomas), and endocrine-inactive ( n = 18)...
July 3, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Kristina Daniūnaitė, Sonata Jarmalaitė, Edita Kriukienė
Tumor-derived DNA, found in body fluids (liquid biopsy) of cancer patients as part of cell-free DNA (cfDNA), lends itself for noninvasive cancer detection and monitoring. Advantages of cfDNA as analytical target have evoked a burst of sophisticated techniques, providing clinically relevant information. Each cell type carries a unique DNA modification profile consisting mainly of patterns of 5-methylcytosine in CpG dinucleotides, which are critical for establishing and maintaining cellular identity and which are frequently disturbed in cancer...
August 3, 2018: Current Opinion in Biotechnology
Pang-Kuo Lo, Qun Zhou
Epigenomics encompasses studies of the chemical modifications of genomic DNA and associated histones, interactions between genomic DNA sequences and proteins, the dynamics of the chromosomal conformation, the functional relationships between these epigenetic events, and the regulatory impacts of these epigenetic events on gene expression in cells. In comparison to current techniques that are only capable of characterizing average epigenomic features across bulk cell ensembles, single-cell epigenomic methodologies are emerging as powerful new techniques to study cellular plasticity and heterogeneity, as seen in stem cells and cancer...
2018: Journal of clinical genomics
Khong-Loon Tiong, Chen-Hsiang Yeang
Most cancer driver genes are involved in generic cellular processes such as DNA repair, cell proliferation and cell adhesion, yet their mutations are often confined to specific cancer types. To resolve this paradox, we explained mutation frequencies of selected genes across tumor types with four features in the corresponding normal tissues from cancer-free subjects: mRNA expression and chromatin accessibility of mutated genes, mRNA expressions of their neighbors in curated pathways and the protein-protein interaction network...
July 30, 2018: Scientific Reports
Suprateek Kundu, Yichen Cheng, Minsuk Shin, Ganiraju Manyam, Bani K Mallick, Veerabhadran Baladandayuthapani
Significant advances in biotechnology have allowed for simultaneous measurement of molecular data across multiple genomic, epigenomic and transcriptomic levels from a single tumor/patient sample. This has motivated systematic data-driven approaches to integrate multi-dimensional structured datasets, since cancer development and progression is driven by numerous co-ordinated molecular alterations and the interactions between them. We propose a novel multi-scale Bayesian approach that combines integrative graphical structure learning from multiple sources of data with a variable selection framework-to determine the key genomic drivers of cancer progression...
2018: PloS One
José M Matés, José A Campos-Sandoval, Javier Márquez
Altered cellular metabolism is a hallmark of cancer. Cancer cells express isoforms of metabolic enzymes that may constitute therapeutic targets. Glutaminase controls glutamine metabolism and their expression correlate with malignancy of tumours. The two types of glutaminase isoenzymes, GLS and GLS2, differ in their expression patterns and functional roles: GLS has oncogenic properties and GLS2 has been described as a tumour suppressor factor. Selective genomic and epigenomic intervention over glutaminase affects the metabolic reprogramming of cancer...
July 24, 2018: Biochimica et Biophysica Acta
Tu Huang, Xiu Peng, Zhenxia Li, Quan Zhou, Shishu Huang, Yuting Wang, Juan Li, Youqiang Song
Owing to the development of new technologies, the epigenome, a second dimensional method for genome analysis has emerged. Epigenetic mechanisms, including DNA methylation, histone modifications and noncoding RNAs, regulate gene expression without changing the genetic sequence. These epigenetic mechanisms normally modulate gene expression, trans-generational effects and inherited expression states in various biological processes. Abnormal epigenetic patterns typically cause pathological conditions, including cancers, age-related diseases, and specific cartilage and bone diseases...
July 26, 2018: Genetics Research
Gaylor Boulay, Angela Volorio, Sowmya Iyer, Liliane C Broye, Ivan Stamenkovic, Nicolo Riggi, Miguel N Rivera
Various types of repetitive sequences are dysregulated in cancer. In Ewing sarcoma, the oncogenic fusion protein EWS-FLI1 induces chromatin features typical of active enhancers at GGAA microsatellite repeats, but the function of these sites has not been directly demonstrated. Here, by combining nascent transcription profiling with epigenome editing, we found that a subset of GGAA microsatellite repeats is transcriptionally active in Ewing sarcoma and that silencing individual repeats abolishes local nascent transcription and leads to markedly reduced expression of putative target genes...
August 1, 2018: Genes & Development
Darren K Patten, Giacomo Corleone, Balázs Győrffy, Ylenia Perone, Neil Slaven, Iros Barozzi, Edina Erdős, Alina Saiakhova, Kate Goddard, Andrea Vingiani, Sami Shousha, Lőrinc Sándor Pongor, Dimitri J Hadjiminas, Gaia Schiavon, Peter Barry, Carlo Palmieri, Raul C Coombes, Peter Scacheri, Giancarlo Pruneri, Luca Magnani
The degree of intrinsic and interpatient phenotypic heterogeneity and its role in tumor evolution is poorly understood. Phenotypic drifts can be transmitted via inheritable transcriptional programs. Cell-type specific transcription is maintained through the activation of epigenetically defined regulatory regions including promoters and enhancers. Here we have annotated the epigenome of 47 primary and metastatic estrogen-receptor (ERα)-positive breast cancer clinical specimens and inferred phenotypic heterogeneity from the regulatory landscape, identifying key regulatory elements commonly shared across patients...
July 23, 2018: Nature Medicine
Kokiladevi Alagarswamy, Ken-Ichi Shinohara, Shihori Takayanagi, Masaki Fukuyo, Atsushi Okabe, Bahityar Rahmutulla, Natsumi Yoda, Rui Qin, Naoki Shiga, Masahiro Sugiura, Hiroaki Sato, Kazuko Kita, Takayoshi Suzuki, Tetsuhiro Nemoto, Atsushi Kaneda
Epigenome regulates gene expression to determine cell fate, and accumulation of epigenomic aberrations leads to diseases, including cancer. NCD38 inhibits lysine-specific demethylase-1 (LSD1), a histone demethylase targeting H3K4me1 and H3K4me2, but not H3K4me3. In this study, we conjugated NCD38 with a potent small molecule called pyrrole (Py) imidazole (Im) polyamide, to analyze whether targets of the inhibitor could be regulated in a sequence-specific manner. We synthesized two conjugates using β-Ala (β) as a linker, i...
June 29, 2018: Oncotarget
Miguel H Bronchud
Placental immune editing switches (PIES) have not evolved to prevent or to cause cancer but to make feto-maternal immune tolerance possible, which is at the very core of our placental mammalian ('Eutherian') nature. Aggressive epithelial cancers might be an unfortunate 'side effect' of this highly sophisticated biological nature. Microenvironmental properties in the placenta and decidua are thought to be a key to feto-maternal immune tolerance. Recently, in 2016-2018, we published the first human genomic and epigenomic evidence of similar gene expression profiles in immune regulatory genes in cancer (primary lobular infiltrating breast cancer and ipsilateral axillary metastatic lymph nodes) and both placenta and decidua of the same young patient with breast carcinoma during pregnancy...
2018: Ecancermedicalscience
Sabrina Grasse, Matthias Lienhard, Steffen Frese, Martin Kerick, Anne Steinbach, Christina Grimm, Michelle Hussong, Jana Rolff, Michael Becker, Felix Dreher, Uwe Schirmer, Stefan Boerno, Anna Ramisch, Gunda Leschber, Bernd Timmermann, Christian Grohé, Heike Lüders, Martin Vingron, Iduna Fichtner, Sebastian Klein, Margarete Odenthal, Reinhard Büttner, Hans Lehrach, Holger Sültmann, Ralf Herwig, Michal R Schweiger
BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related deaths worldwide and is primarily treated with radiation, surgery, and platinum-based drugs like cisplatin and carboplatin. The major challenge in the treatment of NSCLC patients is intrinsic or acquired resistance to chemotherapy. Molecular markers predicting the outcome of the patients are urgently needed. METHODS: Here, we employed patient-derived xenografts (PDXs) to detect predictive methylation biomarkers for platin-based therapies...
July 20, 2018: Genome Medicine
Di Wu, Di Hu, Hao Chen, Guoming Shi, Irfete S Fetahu, Feizhen Wu, Kimberlie Rabidou, Rui Fang, Li Tan, Shuyun Xu, Hang Liu, Christian Argueta, Lei Zhang, Fei Mao, Guoquan Yan, Jiajia Chen, Zhaoru Dong, Ruitu Lv, Yufei Xu, Mei Wang, Yong Ye, Shike Zhang, Danielle Duquette, Songmei Geng, Clark Yin, Christine Guo Lian, George F Murphy, Gail K Adler, Rajesh Garg, Lydia Lynch, Pengyuan Yang, Yiming Li, Fei Lan, Jia Fan, Yang Shi, Yujiang Geno Shi
Diabetes is a complex metabolic syndrome that is characterized by prolonged high blood glucose levels and frequently associated with life-threatening complications1,2 . Epidemiological studies have suggested that diabetes is also linked to an increased risk of cancer3-5 . High glucose levels may be a prevailing factor that contributes to the link between diabetes and cancer, but little is known about the molecular basis of this link and how the high glucose state may drive genetic and/or epigenetic alterations that result in a cancer phenotype...
July 2018: Nature
Lili Li, Brigette B Y Ma, Anthony T C Chan, Francis K L Chan, Paul Murray, Qian Tao
: Cancer genome studies of Epstein-Barr virus (EBV)-associated tumors, including lymphoepithelioma-like carcinomas (LELC) of nasopharyngeal (NPC), gastric (EBVaGC) and lung tissues, and natural killer (NK)/T-cell lymphoma (NKTCL), reveal a unique feature of genomic alterations with fewer gene mutations detected than other common cancers. It is known now that epigenetic alterations play a critical role in the pathogenesis of EBV-associated tumors. As an oncogenic virus, EBV establishes its latent and lytic infections in B-lymphoid and epithelial cells, utilizing hijacked cellular epigenetic machinery...
July 18, 2018: Pathogens
Pei-Fen Kuan, Zhongyuan Mi, Panos Georgopoulos, Dana Hashim, Benjamin J Luft, Paolo Boffetta
DNA methylation has emerged as a promising target linking environmental exposures and cancer. The World Trade Center (WTC) responders sustained exposures to potential carcinogens, resulting in an increased risk of cancer. Previous studies of cancer risk in WTC-exposed responders were limited by the deficiency in quantitative and individual information on exposure to carcinogens. The current study introduces a new exposure-ranking index (ERI) for estimating cancer-related acute and chronic exposures, which aimed to improve the ability of future analyses to estimate cancer risk...
July 11, 2018: European Journal of Cancer Prevention
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