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Cancer epigenomics

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https://www.readbyqxmd.com/read/29345757/whole-genome-sequencing-analysis-for-cancer-genomics-and-precision-medicine
#1
REVIEW
Hidewaki Nakagawa, Masashi Fujita
Explosive advances of next-generation sequencer (NGS) and computational analyses have been exploring somatic protein-altered mutations in most cancer types and these coding mutation data are intensively accumulated. However, there is limited information on somatic mutations in non-coding regions including introns, regulatory elements, and non-coding RNAs, structural variants and pathogen in cancer genomes remain widely unexplored. Whole genome sequencing (WGS) approaches can comprehensively explore all types of genomic alterations in cancer and help us to better understand the whole landscape of driver mutations and mutational signature in cancer genomes and elucidate functional or clinical implications of these unexplored genomic regions and mutational signature...
January 18, 2018: Cancer Science
https://www.readbyqxmd.com/read/29344347/epigenetic-alterations-in-tramp-mice-epigenome-dna-methylation-profiling-using-medip-seq
#2
Wenji Li, Ying Huang, Davit Sargsyan, Tin Oo Khor, Yue Guo, Limin Shu, Anne Yuqing Yang, Chengyue Zhang, Ximena Paredes-Gonzalez, Michael Verzi, Ronald P Hart, Ah-Ng Kong
Purpose: We investigated the genomic DNA methylation profile of prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model and to analyze the crosstalk among targeted genes and the related functional pathways. Methods: Prostate DNA samples from 24-week-old TRAMP and C57BL/6 male mice were isolated. The DNA methylation profiles were analyzed by methylated DNA immunoprecipitation (MeDIP) followed by next-generation sequencing (MeDIP-seq)...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29333921/targeting-brd4-proteins-suppresses-the-growth-of-nsclc-through-downregulation-of-eif4e-expression
#3
Zhongyuan Gao, Ting Yuan, Xiao Zhou, Ping Ni, Geng Sun, Ping Li, Zhixiang Cheng, Xuerong Wang
Lung cancer is the leading cause of cancer-related death worldwide. Bromodomain and extraterminal domain (BET) proteins act as epigenome readers for gene transcriptional regulation. Among BET family members, BRD4 was well studied, but for its mechanism in non-small cell lung carcinoma has not been elucidated. eIF4E regulates gene translation and has been proved to play an important role in the progression of lung cancer. In this study, we first confirmed that BET inhibitors JQ1 and I-BET151 suppressed the growth of NSCLCs, in parallel with downregulated eIF4E expression...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29325224/hereditary-kidney-cancer-syndromes-genetic-disorders-driven-by-alterations-in-metabolism-and-epigenome-regulation
#4
Hisashi Hasumi, Masahiro Yao
Although hereditary kidney cancer syndrome accounts for around five percent of all kidney cancers, the mechanistic insight into tumor development in these rare conditions has provided the foundation for the development of molecular targeting agents currently used for sporadic kidney cancer. In the late 1980s, the comprehensive study for hereditary kidney cancer syndrome was launched in the National Cancer Institute, U.S.A. and the first kidney cancer associated gene, VHL was identified through kindred analysis of von Hippel-Lindau syndrome in 1993...
January 11, 2018: Cancer Science
https://www.readbyqxmd.com/read/29322925/subtype-identification-from-heterogeneous-tcga-datasets-on-a-genomic-scale-by-multi-view-clustering-with-enhanced-consensus
#5
Menglan Cai, Limin Li
BACKGROUND: The Cancer Genome Atlas (TCGA) has collected transcriptome, genome and epigenome information for over 20 cancers from thousands of patients. The availability of these diverse data types makes it necessary to combine these data to capture the heterogeneity of biological processes and phenotypes and further identify homogeneous subtypes for cancers such as breast cancer. Many multi-view clustering approaches are proposed to discover clusters across different data types. The problem is challenging when different data types show poor agreement of clustering structure...
December 21, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/29315108/review-of-molecular-classification-and-treatment-implications-of-pediatric-brain-tumors
#6
Ana S Guerreiro Stucklin, Vijay Ramaswamy, Craig Daniels, Michael D Taylor
PURPOSE OF REVIEW: Brain tumors are the most common solid tumors and leading cause of cancer-related death in children. The advent of large-scale genomics has resulted in a plethora of profiling studies that have mapped the genetic and epigenetic landscapes of pediatric brain tumors, ringing in a new era of precision diagnostics and targeted therapies. In this review, we highlight the most recent findings, focusing on studies published after 2015, and discuss how new evidence is changing the care of children with brain tumors...
February 2018: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29310839/decoding-colorectal-cancer-epigenomics
#7
REVIEW
Khalid El Bairi, Kanwal Tariq, Imane Himri, Abdeslam Jaafari, Wiam Smaili, Abdul Hafeez Kandhro, Adel Gouri, Bouchra Ghazi
Colorectal cancer (CRC) is very heterogeneous and presents different types of epigenetic alterations including DNA methylation, histone modifications and microRNAs. These changes are considered as characteristics of various observed clinical phenotypes. Undoubtedly, the discovery of epigenetic pathways with novel epigenetic-related mechanisms constitutes a promising advance in cancer biomarker discovery. In this review, we provide an evidence-based discussing of the current understanding of CRC epigenomics and its role in initiation, epithelial-to-mesenchymal transition and metastasis...
January 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29309643/androgen-receptor-splice-variants-bind-to-constitutively-open-chromatin-and-promote-abiraterone-resistant-growth-of-prostate-cancer
#8
Yundong He, Ji Lu, Zhenqing Ye, Siyuan Hao, Liewei Wang, Manish Kohli, Donald J Tindall, Benyi Li, Runzhi Zhu, Liguo Wang, Haojie Huang
Androgen receptor (AR) splice variants (ARVs) are implicated in development of castration-resistant prostate cancer (CRPC). Upregulation of ARVs often correlates with persistent AR activity after androgen deprivation therapy (ADT). However, the genomic and epigenomic characteristics of ARV-dependent cistrome and the disease relevance of ARV-mediated transcriptome remain elusive. Through integrated chromatin immunoprecipitation coupled sequencing (ChIP-seq) and RNA sequencing (RNA-seq) analysis, we identified ARV-preferential-binding sites (ARV-PBS) and a set of genes preferentially transactivated by ARVs in CRPC cells...
January 4, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29302578/epigenomic-hard-drive-imprinting-a-hidden-code-beyond-the-biological-death-of-cancer-patients
#9
REVIEW
Pritish Nilendu, Nilesh Kumar Sharma
Several genetic and epigenetic theories have been suggested to explain the intricacies of life and death. However, several questions remain unsettled regarding cellular death events, particularly of living tissue in the case of cancer patients, such as the fate and adaptation of cancer cells after biological death. It is possible that cancer cells can display the intent to communicate with the external environment after biological death by means of molecular, genetic, and epigenetic pathways. Whether these cancer cells contain special information in the form of coding that may help them survive beyond the biological death of cancer patients is unknown...
December 2017: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/29290541/genomic-and-epigenomic-profiling-of-high-risk-intestinal-metaplasia-reveals-molecular-determinants-of-progression-to-gastric-cancer
#10
Kie Kyon Huang, Kalpana Ramnarayanan, Feng Zhu, Supriya Srivastava, Chang Xu, Angie Lay Keng Tan, Minghui Lee, Suting Tay, Kakoli Das, Manjie Xing, Aliya Fatehullah, Syed Muhammad Fahmy Alkaff, Tony Kiat Hon Lim, Jonathan Lee, Khek Yu Ho, Steven George Rozen, Bin Tean Teh, Nick Barker, Chung King Chia, Christopher Khor, Choon Jin Ooi, Kwong Ming Fock, Jimmy So, Wee Chian Lim, Khoon Lin Ling, Tiing Leong Ang, Andrew Wong, Jaideepraj Rao, Andrea Rajnakova, Lee Guan Lim, Wai Ming Yap, Ming Teh, Khay Guan Yeoh, Patrick Tan
Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We performed (epi)genomic profiling of 138 IMs from 148 cancer-free patients, recruited through a 10-year prospective study. Compared with GCs, IMs exhibit low mutational burdens, recurrent mutations in certain tumor suppressors (FBXW7) but not others (TP53, ARID1A), chromosome 8q amplification, and shortened telomeres. Sequencing identified more IM patients with active Helicobacter pylori infection compared with histopathology (11%-27%)...
December 26, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29288495/pan-cancer-insights-from-the-cancer-genome-atlas-the-pathologist-s-perspective
#11
REVIEW
Lee A D Cooper, Elizabeth G Demicco, Joel H Saltz, Reid T Powell, Arvind Rao, Alexander J Lazar
The Cancer Genome Atlas (TCGA) represents one of several international consortia dedicated to performing comprehensive genomic and epigenomic analyses of selected tumor types to advance understanding of disease and provide an open-access resource for worldwide cancer research. Thirty-three tumor types (selected by histology or tissue of origin, to include both common and rare diseases), comprising over 11,000 specimens were subjected to DNA sequencing, copy number and methylation analysis, and transcriptomic, proteomic, and histologic evaluation...
December 30, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29286410/an-engineered-split-tet2-enzyme-for-chemical-inducible-dna-hydroxymethylation-and-epigenetic-remodeling
#12
Minjung Lee, Yubin Zhou, Yun Huang
DNA methylation is a stable and heritable epigenetic modification in the mammalian genome and is involved in regulating gene expression to control cellular functions. The reversal of DNA methylation, or DNA demethylation, is mediated by the ten-eleven translocation (TET) protein family of dioxygenases. Although it has been widely reported that aberrant DNA methylation and demethylation are associated with developmental defects and cancer, how these epigenetic changes directly contribute to the subsequent alteration in gene expression or disease progression remains unclear, largely owing to the lack of reliable tools to accurately add or remove DNA modifications in the genome at defined temporal and spatial resolution...
December 18, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29285267/a-molecular-signature-of-lung-cancer-potential-biomarkers-for-adenocarcinoma-and-squamous-cell-carcinoma
#13
Varda Shoshan-Barmatz, Yael Bishitz, Avijit Paul, Yakov Krelin, Itay Nakdimon, Nir Peled, Avia Lavon, Elina Rudoy-Zilberman, Yael Refaely
Adenocarcinoma (AC) and squamous cell carcinoma (SCC), sub-types of non-small cell lung cancer (NSCLC), both present unique features at the genome, epigenome, transcriptome and proteome levels, as well as shared clinical and histopathological characteristics, but differ in terms of treatment. To ensure proper treatment, one must be able to distinguish between these sub-types. Here, we identify novel biomarker proteins in NSCLC, allowing for distinguishing between the AC and SCC sub-types. Proteomics analysis distinguished between healthy and tumor tissues, with the expression level of 1,494 proteins being altered, 378 of which showed a ≥|100|-fold change...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29282690/targeting-the-epigenome-as-a-novel-therapeutic-approach-for-breast-cancer
#14
Sumin Oh, Je Yeong Ko, Chaeun Oh, Kyung Hyun Yoo
Breast cancer is one of complex diseases that are influenced by environment. Various genetic and epigenetic alterations are provoking causes of breast carcinogenesis. Dynamic epigenetic regulation including DNA methylation and histone modification induces dysregulation of genes related to proliferation, apoptosis, and metastasis in breast cancer. DNA methylation is strongly associated with the repression of transcription through adding to the methyl group by DNA methyltransferases (DNMTs), and tumor suppressor genes such as CCND2 and RUNX3 have been investigated to undergo hypermethylation at promoter region in breast cancer...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29281093/large-scale-determination-and-characterization-of-cell-type-specific-regulatory-elements-in-the-human-genome
#15
Can Wang, Shihua Zhang
Histone modifications have been widely elucidated to play vital roles in gene regulation and cell identity. The Roadmap Epigenomics Consortium generated a reference catalogue of several key histone modifications across > 100s of human cell types and tissues. Decoding these epigenomes into functional regulatory elements is a challenging task in computational biology. To this end, we adopted a differential chromatin modification analysis framework to comprehensively determine and characterize cell type-specific regulatory elements (CSREs) and their histone modification codes in the human epigenomes of five histone modifications across 127 tissues or cell types...
December 21, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29277749/cancer-progenitor-cells-the-result-of-an-epigenetic-event
#16
REVIEW
Karolina Lapinska, Gabriela Faria, Sandra McGonagle, Kate Morgan Macumber, Sarah Heerboth, Sibaji Sarkar
The concept of cancer stem cells was proposed in the late 1990s. Although initially the idea seemed controversial, the existence of cancer stem cells is now well established. However, the process leading to the formation of cancer stem cells is still not clear and thus requires further research. This article discusses epigenetic events that possibly produce cancer progenitor cells from predisposed cells by the influence of their environment. Every somatic cell possesses an epigenetic signature in terms of histone modifications and DNA methylation, which are obtained during lineage-specific differentiation of pluripotent stem cells, which is specific to that particular tissue...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29275361/applications-of-support-vector-machine-svm-learning-in-cancer-genomics
#17
REVIEW
Shujun Huang, Nianguang Cai, Pedro Penzuti Pacheco, Shavira Narandes, Yang Wang, Wayne Xu
Machine learning with maximization (support) of separating margin (vector), called support vector machine (SVM) learning, is a powerful classification tool that has been used for cancer genomic classification or subtyping. Today, as advancements in high-throughput technologies lead to production of large amounts of genomic and epigenomic data, the classification feature of SVMs is expanding its use in cancer genomics, leading to the discovery of new biomarkers, new drug targets, and a better understanding of cancer driver genes...
January 2018: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/29273624/enhancer-transcription-reveals-subtype-specific-gene-expression-programs-controlling-breast-cancer-pathogenesis
#18
Hector L Franco, Anusha Nagari, Venkat S Malladi, Wenqian Li, Yuanxin Xi, Dana Richardson, Kendra L Allton, Kaori Tanaka, Jing Li, Shino Murakami, Khandan Keyomarsi, Mark T Bedford, Xiaobing Shi, Wei Li, Michelle C Barton, Sharon Y R Dent, W Lee Kraus
Noncoding transcription is a defining feature of active enhancers, linking transcription factor (TF) binding to the molecular mechanisms controlling gene expression. To determine the relationship between enhancer activity and biological outcomes in breast cancers, we profiled the transcriptomes (using GRO-seq and RNA-seq) and epigenomes (using ChIP-seq) of 11 different human breast cancer cell lines representing five major molecular subtypes of breast cancer, as well as two immortalized ("normal") human breast cell lines...
December 22, 2017: Genome Research
https://www.readbyqxmd.com/read/29246759/metabolic-control-of-cd8-t-cell-fate-decisions-and-antitumor-immunity
#19
REVIEW
Lianjun Zhang, Pedro Romero
CD8+ T cells are central players in controlling infections and cancer. Longevity, functionality, and metabolic fitness are critical determinants of T cell efficacy in cancer immunotherapy. Tumor-infiltrating CD8+ T cells undergo metabolic 'exhaustion' in the nutrient- and oxygen-deprived tumor microenvironment (TME). Thus, reprograming CD8+ T cell metabolism may provide important therapeutic strategies for cancer treatment. Indeed, the adoptive transfer of memory CD8+ T cells with sustained metabolic fitness may yield better antitumor protection in both mouse models and the clinic...
December 12, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29240334/do-in-vitro-fertilization-treatments-result-in-healthy-babies
#20
REVIEW
Noora Kaartinen, Helena Tinkanen
In Finland, the proportion of children born as a result of in vitro fertilization treatments is annually approximately 3.3%, and the percentage proportion of the population is growing. Their general somatic health status and cognitive development do not differ from spontaneously fertilized children. In vitro fertilization treatments are, however, associated with a slightly elevated risk of preterm delivery, low birth weight and structural abnormalities. The risk of childhood cancer does not appear to be increased in IVF children...
2017: Duodecim; Lääketieteellinen Aikakauskirja
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