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Integrative genomics cancer

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https://www.readbyqxmd.com/read/28550453/exchange-of-genetic-sequences-between-viruses-and-hosts
#1
Robin A Weiss
Although genetic transfer between viruses and vertebrate hosts occurs less frequently than gene flow between bacteriophages and prokaryotes, it is extensive and has affected the evolution of both parties. With retroviruses, the integration of proviral DNA into chromosomal DNA can result in the activation of adjacent host gene expression and in the transduction of host transcripts into retroviral genomes as oncogenes. Yet in contrast to lysogenic phage, there is little evidence that viral oncogenes persist in a chain of natural transmission or that retroviral transduction is a significant driver of the horizontal spread of host genes...
May 28, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28549257/human-somatic-cells-deficient-for-rad52-are-impaired-for-viral-integration-and-compromised-for-most-aspects-of-homology-directed-repair
#2
Yinan Kan, Nizar N Batada, Eric A Hendrickson
Homology-directed repair (HDR) maintains genomic integrity by eliminating lesions such as DNA double-strand breaks (DSBs), interstrand crosslinks (ICLs) and stalled replication forks and thus a deficiency in HDR is associated with genomic instability and cancer predisposition. The mechanism of HDR is best understood and most rigorously characterized in yeast. The inactivation of the fungal radiation sensitive 52 (RAD52) gene, which has both recombination mediator and single-strand annealing (SSA) activities in vitro, leads to severe HDR defects in vivo...
May 10, 2017: DNA Repair
https://www.readbyqxmd.com/read/28548087/the-distinct-metabolic-phenotype-of-lung-squamous-cell-carcinoma-defines-selective-vulnerability-to-glycolytic-inhibition
#3
Justin Goodwin, Michael L Neugent, Shin Yup Lee, Joshua H Choe, Hyunsung Choi, Dana M R Jenkins, Robin J Ruthenborg, Maddox W Robinson, Ji Yun Jeong, Masaki Wake, Hajime Abe, Norihiko Takeda, Hiroko Endo, Masahiro Inoue, Zhenyu Xuan, Hyuntae Yoo, Min Chen, Jung-Mo Ahn, John D Minna, Kristi L Helke, Pankaj K Singh, David B Shackelford, Jung-Whan Kim
Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28545026/identification-of-novel-long-non-coding-rna-biomarkers-for-prognosis-prediction-of-papillary-thyroid-cancer
#4
Qiuying Li, Haihong Li, Lu Zhang, Chunming Zhang, Wentao Yan, Chao Wang
Papillary thyroid carcinoma (PTC) is the most frequent type of malignant thyroid tumor. Several lncRNA signatures have been established for prognosis prediction in some cancers. However, the prognostic value of lncRNAs has not been investigated in PTC yet. In this study, we performed genome-wide analysis of lncRNA expression profiles in a large cohort of PTC patients from The Cancer Genome Atlas and identified 111 differentially expressed lncRNAs between tumor and non-tumor samples and between recurrent and recurrence-free samples...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28542811/integrative-analyses-reveal-biological-pathways-and-key-genes-in-psoriasis
#5
J Dou, L Zhang, X Xie, L Ye, C Yang, L Wen, C Shen, C Zhu, S Zhao, Z Zhu, B Liang, Z Wang, H Li, X Fan, S Liu, X Yin, X Zheng, L Sun, S Yang, Y Cui, F Zhou, X Zhang
BACKGROUND: Psoriasis is a complex disease that is influenced by both genetic and environmental factors with abnormal gene expression in lesional skin. However, no studies are available on genome-scale gene expression of psoriatic lesions in the Chinese population. In addition, systematic studies on the biological pathways, pathogenicity and interaction networks of psoriasis-related genes with abnormal expression profiles require further investigation. OBJECTIVES: To further explore the associated pathways in psoriasis by functional analysis and to identify the key genes by gene pathogenicity analysis...
May 25, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28541389/cell-cycle-dependent-control-of-homologous-recombination
#6
Xin Zhao, Chengwen Wei, Jingjing Li, Poyuan Xing, Jingyao Li, Sihao Zheng, Xuefeng Chen
DNA double-strand breaks (DSBs) are among the most deleterious type of DNA lesions threatening genome integrity. Homologous recombination (HR) and non-homologous end joining (NHEJ) are two major pathways to repair DSBs. HR requires a homologous template to direct DNA repair, and is generally recognized as a high-fidelity pathway. In contrast, NHEJ directly seals broken ends, but the repair product is often accompanied by sequence alterations. The choice of repair pathways is strictly controlled by the cell cycle...
May 25, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28541380/a-fully-bayesian-latent-variable-model-for-integrative-clustering-analysis-of-multi-type-omics-data
#7
Qianxing Mo, Ronglai Shen, Cui Guo, Marina Vannucci, Keith S Chan, Susan G Hilsenbeck
Identification of clinically relevant tumor subtypes and omics signatures is an important task in cancer translational research for precision medicine. Large-scale genomic profiling studies such as The Cancer Genome Atlas (TCGA) Research Network have generated vast amounts of genomic, transcriptomic, epigenomic, and proteomic data. While these studies have provided great resources for researchers to discover clinically relevant tumor subtypes and driver molecular alterations, there are few computationally efficient methods and tools for integrative clustering analysis of these multi-type omics data...
May 24, 2017: Biostatistics
https://www.readbyqxmd.com/read/28540673/micrornas-long-noncoding-rnas-and-their-functions-in-human-disease
#8
Min Xue, Ying Zhuo, Bin Shan
Majority of the human genome is transcribed into RNAs with absent or limited protein-coding potential. microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are two major families of the non-protein-coding transcripts. miRNAs and lncRNAs can regulate fundamental cellular processes via diverse mechanisms. The expression and function of miRNAs and lncRNAs are tightly regulated in development and physiological homeostasis. Dysregulation of miRNAs and lncRNAs is critical to pathogenesis of human disease. Moreover, recent evidence indicates a cross talk between miRNAs and lncRNAs...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28536537/-gestaltomics-systems-biology-schemes-for-the-study-of-neuropsychiatric-diseases
#9
REVIEW
Nora A Gutierrez Najera, Osbaldo Resendis-Antonio, Humberto Nicolini
The integration of different sources of biological information about what defines a behavioral phenotype is difficult to unify in an entity that reflects the arithmetic sum of its individual parts. In this sense, the challenge of Systems Biology for understanding the "psychiatric phenotype" is to provide an improved vision of the shape of the phenotype as it is visualized by "Gestalt" psychology, whose fundamental axiom is that the observed phenotype (behavior or mental disorder) will be the result of the integrative composition of every part...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28533502/clinical-value-and-prospective-pathway-signaling-of-microrna-375-in-lung-adenocarcinoma-a-study-based-on-the-cancer-genome-atlas-tcga-gene-expression-omnibus-geo-and-bioinformatics-analysis
#10
Ting-Qing Gan, Wen-Jie Chen, Hui Qin, Su-Ning Huang, Li-Hua Yang, Ye-Ying Fang, Lin-Jiang Pan, Zu-Yun Li, Gang Chen
BACKGROUND Lung adenocarcinoma (LUAD) is the most frequent lung cancer. MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis of LUAD. Although miRNAs are broadly recognized in LUAD, the role of microRNA-375 in LUAD is still not fully elucidated. MATERIAL AND METHODS We evaluated the significance of miR-375 expression in LUAD by using analysis of a public dataset from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database and a literature review. Furthermore, we investigated the biological function of miR-375 by gene ontology enrichment and target prediction analysis...
May 23, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28532404/use-of-the-qiagen-genereader-ngs-system-for-detection-of-kras-mutations-validated-by-the-qiagen-therascreen-pcr-kit-and-alternative-ngs-platform
#11
Agus Darwanto, Anne-Mette Hein, Sascha Strauss, Yi Kong, Andrew Sheridan, Dan Richards, Eric Lader, Monika Ngowe, Timothy Pelletier, Danielle Adams, Austin Ricker, Nishit Patel, Andreas Kühne, Simon Hughes, Dan Shiffman, Dirk Zimmermann, Kai Te Kaat, Thomas Rothmann
BACKGROUND: The detection of somatic mutations in primary tumors is critical for the understanding of cancer evolution and targeting therapy. Multiple technologies have been developed to enable the detection of such mutations. Next generation sequencing (NGS) is a new platform that is gradually becoming the technology of choice for genotyping cancer samples, owing to its ability to simultaneously interrogate many genomic loci at massively high efficiency and increasingly lower cost. However, multiple barriers still exist for its broader adoption in clinical research practice, such as fragmented workflow and complex bioinformatics analysis and interpretation...
May 22, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28530655/a-quantitative-and-multiplexed-approach-to-uncover-the-fitness-landscape-of-tumor-suppression-in-vivo
#12
Zoë N Rogers, Christopher D McFarland, Ian P Winters, Santiago Naranjo, Chen-Hua Chuang, Dmitri Petrov, Monte M Winslow
Cancer growth is a multistage, stochastic evolutionary process. While cancer genome sequencing has been instrumental in identifying the genomic alterations that occur in human tumors, the consequences of these alterations on tumor growth remain largely unexplored. Conventional genetically engineered mouse models enable the study of tumor growth in vivo, but they are neither readily scalable nor sufficiently quantitative to unravel the magnitude and mode of action of many tumor-suppressor genes. Here, we present a method that integrates tumor barcoding with ultradeep barcode sequencing (Tuba-seq) to interrogate tumor-suppressor function in mouse models of human cancer...
May 22, 2017: Nature Methods
https://www.readbyqxmd.com/read/28528358/dna-topoisomerase-targeting-chemotherapeutics-what-s-new
#13
REVIEW
Selma M Cuya, Mary-Ann Bjornsti, Robert C A M van Waardenburg
To resolve the topological problems that threaten the function and structural integrity of nuclear and mitochondrial genomes and RNA molecules, human cells encode six different DNA topoisomerases including type IB enzymes (TOP1 and TOP1mt), type IIA enzymes (TOP2α and TOP2β) and type IA enzymes (TOP3α and TOP3β). DNA entanglements and the supercoiling of DNA molecules are regulated by topoisomerases through the introduction of transient enzyme-linked DNA breaks. The covalent topoisomerase-DNA complexes are the cellular targets of a diverse group of cancer chemotherapeutics, which reversibly stabilize these reaction intermediates...
May 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28522810/integrative-analysis-of-genomic-sequencing-data-reveals-higher-prevalence-of-lrp1b-mutations-in-lung-adenocarcinoma-patients-with-copd
#14
Dakai Xiao, Fuqiang Li, Hui Pan, Han Liang, Kui Wu, Jianxing He
Both chronic Obstruction Pulmonary Disease (COPD) and lung cancer are leading causes of death globally. Although COPD and lung cancer coexist frequently, it is unknown whether lung cancer patients with COPD harbor distinct genomic characteristics compared to those without COPD. In this study, we retrospectively analyzed genomic sequencing data from 272 patients with lung adenocarcinoma (LUAD) and compared the genetic alterations in LUAD patients with and without COPD. Integrative analysis of whole-genome and exome sequencing data revealed that COPD and non-COPD groups showed high concordance in mutational burden and spectra...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522256/sporadic-early-onset-diffuse-gastric-cancers-have-high-frequency-of-somatic-cdh1-alterations-but-low-frequency-of-somatic-rhoa-mutations-compared-with-late-onset-cancers
#15
Soo Young Cho, Jun Won Park, Yang Liu, Young Soo Park, Ju Hee Kim, Hanna Yang, Hyejin Um, Woo Ri Ko, Byung Il Lee, Sun Young Kwon, Seung Wan Ryu, Chae Hwa Kwon, Do Youn Park, Jae-Hyuk Lee, Sang Il Lee, Kyu Sang Song, Hoon Hur, Sang-Uk Han, Heekyung Chang, Su-Jin Kim, Byung-Sik Kim, Jeong-Hwan Yook, Moon-Won Yoo, Beom-Su Kim, In-Seob Lee, Myeong-Cherl Kook, Nina Thiessen, An He, Chip Stewart, Andrew Dunford, Jaegil Kim, Juliann Shih, Gordon Saksena, Andrew D Cherniack, Steven Schumacher, Amaro-Taylor Weiner, Mara Rosenberg, Gad Getz, Eun Gyeong Yang, Min Hee Ryu, Adam J Bass, Hark Kyun Kim
BACKGROUND & AIMS: Early-onset gastric cancer, which develops in younger patients than most gastric cancers, is usually detected at advanced stages, has diffuse histologic features, and occurs more frequently in women. We investigated somatic genomic alterations associated with the unique characteristics of sporadic diffuse gastric cancers (DGCs) from younger patients. METHODS: We conducted whole exome and RNA sequence analyses of 80 resected DGC samples from patients 45 years old or younger in Korea...
May 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28521532/new-antivirals-for-the-treatment-of-chronic-hepatitis-b
#16
Vincent Soriano, Pablo Barreiro, Laura Benitez, Jose M Peña, Carmen de Mendoza
Current treatment with oral nucleos(t)ides entecavir or tenofovir provide sustained suppression of HBV replication and clinical benefit in most chronic hepatitis B virus (HBV) infected persons. However, HBV rebound generally occurs upon drug discontinuation due to persistence of genomic HBV reservoirs as episomic cccDNA and chromosomic integrated HBV-DNA. There is renewed enthusiasm on HBV drug discovery following recent successes with antivirals for hepatitis C and immunotherapies for some cancers. Areas covered: New drugs that target distinct steps of the HBV life cycle are been developed, including inhibitors of viral entry, new polymerase inhibitors, capsid and assembly inhibitors, virus release blockers, and disruptors of cccDNA formation and transcription...
May 18, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28521423/molecular-dysexpression-in-gastric-cancer-revealed-by-integrated-analysis-of-transcriptome-data
#17
Xiaomei Li, Weiwei Dong, Xueling Qu, Huixia Zhao, Shuo Wang, Yixin Hao, Qiuwen Li, Jianhua Zhu, Min Ye, Wenhua Xiao
Gastric cancer (GC) is often diagnosed in the advanced stages and is associated with a poor prognosis. Obtaining an in depth understanding of the molecular mechanisms of GC has lagged behind compared with other cancers. This study aimed to identify candidate biomarkers for GC. An integrated analysis of microarray datasets was performed to identify differentially expressed genes (DEGs) between GC and normal tissues. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then performed to identify the functions of the DEGs...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521287/5azadc-treatment-upregulates-mir-375-level-and-represses-hpv16-e6-expression
#18
Adrien Morel, Aurélie Baguet, Jérôme Perrard, Caroline Demeret, Elise Jacquin, David Guenat, Christiane Mougin, Jean-Luc Prétet
High risk human papillomaviruses are the etiological agents of cervical cancer and HPV16 is the most oncogenic genotype. Immortalization and transformation of infected cells requires the overexpression of the two viral oncoproteins E6 and E7 following HPV DNA integration into the host cell genome. Integration often leads to the loss of the E2 open reading frame and the corresponding protein can no longer act as a transcriptional repressor on p97 promoter. Recently, it has been proposed that long control region methylation also contributes to the regulation of E6/E7 expression...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28520848/pattern-fusion-analysis-by-adaptive-alignment-of-multiple-heterogeneous-omics-data
#19
Qianqian Shi, Chuanchao Zhang, Minrui Peng, Xiangtian Yu, Tao Zeng, Juan Liu, Luonan Chen
Motivation: Integrating different omics profiles is a challenging task, which provides a comprehensive way to understand complex diseases in a multi-view manner. One key for such an integration is to extract intrinsic patterns in concordance with data structures, so as to discover consistent information across various data types even with noise pollution. Thus, we proposed a novel framework called "pattern fusion analysis" (PFA), which performs automated information alignment and bias correction, to fuse local sample-patterns (e...
May 18, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28520777/network-based-stratification-of-major-cancers-by-integrating-somatic-mutation-and-gene-expression-data
#20
Zongzhen He, Junying Zhang, Xiguo Yuan, Zhaowen Liu, Baobao Liu, Shouheng Tuo, Yajun Liu
The stratification of cancer into subtypes that are significantly associated with clinical outcomes is beneficial for targeted prognosis and treatment. In this study, we integrated somatic mutation and gene expression data to identify clusters of patients. In contrast to previous studies, we constructed cancer-type-specific significant co-expression networks (SCNs) rather than using a fixed gene network across all cancers, such as the network-based stratification (NBS) method, which ignores cancer heterogeneity...
2017: PloS One
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