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Integrative genomics cancer

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https://www.readbyqxmd.com/read/29665409/epigenomic-biomarkers-for-prognostication-and-diagnosis-of-gastrointestinal-cancers
#1
REVIEW
Chi Chun Wong, Weilin Li, Bertina Chan, Jun Yu
Altered epigenetic regulation is central to many human diseases, including cancer. Over the past two decade, major advances have been made in our understanding of the role of epigenetic alterations in carcinogenesis, particularly for DNA methylation, histone modifications and non-coding RNAs. Aberrant hypermethylation of DNA at CpG islands is a well-established phenomenon that mediates transcriptional silencing of tumor suppressor genes, and it is an early event integral to gastrointestinal cancer development...
April 14, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29664143/pathway-aggregation-for-survival-prediction-via-multiple-kernel-learning
#2
Jennifer A Sinnott, Tianxi Cai
Attempts to predict prognosis in cancer patients using high-dimensional genomic data such as gene expression in tumor tissue can be made difficult by the large number of features and the potential complexity of the relationship between features and the outcome. Integrating prior biological knowledge into risk prediction with such data by grouping genomic features into pathways and networks reduces the dimensionality of the problem and could improve prediction accuracy. Additionally, such knowledge-based models may be more biologically grounded and interpretable...
April 17, 2018: Statistics in Medicine
https://www.readbyqxmd.com/read/29662108/nips-a-3d-network-integrated-predictor-of-deleterious-protein-saps-and-its-application-in-cancer-prognosis
#3
Bo Wang, Jing Li, Xi Cheng, Qiao Zhou, Jingxu Yang, Menghuan Zhang, Haifeng Chen, Jing Li
Identifying deleterious mutations remains a challenge in cancer genome sequencing projects, reflecting the vast number of candidate mutations per tumour and the existence of interpatient heterogeneity. Based on a 3D protein interaction network profiled via large-scale cross-linking mass spectrometry, we propose a weighted average formula involving the combination of three types of information into a 'meta-score'. We assume that a single amino acid polymorphism (SAP) may have a deleterious effect if the mutation rarely occurs naturally during evolution, if it inhibits binding between a pair of interacting proteins when located at their interface, or if it plays an important role in a protein interaction (PPI) network...
April 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29661773/integrated-genomic-and-immunophenotypic-classification-of-pancreatic-cancer-reveals-three-distinct-subtypes-with-prognostic-predictive-significance
#4
Martin Wartenberg, Silvia Cibin, Inti Zlobec, Erik Vassella, Serenella M M Eppenberger-Castori, Luigi Terracciano, Micha Eichmann, Mathias Worni, Beat Gloor, Aurel Perren, Eva Karamitopoulou
PURPOSE: Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC-cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. EXPERIMENTAL DESIGN: A well-characterized PDAC-cohort (n=110) underwent next-generation sequencing with a hotspot cancer panel, while Next-generation Tissue-Microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM) and DNA mismatch-repair proteins...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29661228/mir-760-suppresses-human-colorectal-cancer-growth-by-targeting-batf3-ap-1-cyclind1-signaling
#5
Ling Cao, Yulin Liu, Dan Wang, Lan Huang, Feng Li, Jinbo Liu, Chaoqi Zhang, Zhibo Shen, Qun Gao, Weitang Yuan, Yi Zhang
BACKGROUND: Recent studies have reported that microRNAs (miRNAs) often function as negative post-transcriptional regulators with altered expression levels found in colorectal cancer (CRC). There have been few studies on miRNAs that regulate the oncogenic alterations in CRC. Here, we aim to explore the anti-cancer miRNA and the potential mechanisms by which miRNAs modulate CRC progression. METHODS: We performed an integrated analysis of CRC miRNA expression datasets in The Cancer Genome Atlas (TCGA)...
April 16, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29659648/single-gene-prognostic-signatures-for-advanced-stage-serous-ovarian-cancer-based-on-1257-patient-samples
#6
Fan Zhang, Kai Yang, Kui Deng, Yuanyuan Zhang, Weiwei Zhao, Huan Xu, Zhiwei Rong, Kang Li
OBJECTIVE: We sought to identify stable single-gene prognostic signatures based on a large collection of advanced stage serous ovarian cancer (AS-OvCa) gene expression data and explore their functions. METHODS: The empirical Bayes (EB) method was used to remove the batch effect and integrate 8 ovarian cancer datasets. Univariate Cox regression was used to evaluate the association between gene and overall survival (OS). The Database for Annotation, Visualization and Integrated Discovery (DAVID) tool was used for the functional annotation of genes for Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways...
April 16, 2018: Molecular omics
https://www.readbyqxmd.com/read/29658776/toward-recovering-allele-specific-cancer-genome-graphs
#7
Ashok Rajaraman, Jian Ma
Integrated analysis of structural variants (SVs) and copy number alterations in aneuploid cancer genomes is key to understanding tumor genome complexity. A recently developed algorithm, Weaver, can estimate, for the first time, allele-specific copy number of SVs and their interconnectivity in aneuploid cancer genomes. However, one major limitation is that not all SVs identified by Weaver are phased. In this article, we develop a general convex programming framework that predicts the interconnectivity of unphased SVs with possibly noisy allele-specific copy number estimations as input...
April 16, 2018: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://www.readbyqxmd.com/read/29658398/live-cell-imaging-reveals-the-dynamics-and-function-of-single-telomere-terra-molecules-in-cancer-cells
#8
Laura Avogaro, Emmanuelle Querido, Myriam Dalachi, Michael F Jantsch, Pascal Chartrand, Emilio Cusanelli
Telomeres cap the ends of eukaryotic chromosomes, protecting them from degradation and erroneous recombination events which may lead to genome instability. Telomeres are transcribed giving rise to telomeric repeat-containing RNAs, called TERRA. The TERRA long noncoding RNAs have been proposed to play important roles in telomere biology, including heterochromatin formation and telomere length homeostasis. While TERRA RNAs are predominantly nuclear and localize at telomeres, little is known about the dynamics and function of TERRA molecules expressed from individual telomeres...
April 16, 2018: RNA Biology
https://www.readbyqxmd.com/read/29656893/dna-repair-network-analysis-reveals-shieldin-as-a-key-regulator-of-nhej-and-parp-inhibitor-sensitivity
#9
Rajat Gupta, Kumar Somyajit, Takeo Narita, Elina Maskey, Andre Stanlie, Magdalena Kremer, Dimitris Typas, Michael Lammers, Niels Mailand, Andre Nussenzweig, Jiri Lukas, Chunaram Choudhary
Repair of damaged DNA is essential for maintaining genome integrity and for preventing genome-instability-associated diseases, such as cancer. By combining proximity labeling with quantitative mass spectrometry, we generated high-resolution interaction neighborhood maps of the endogenously expressed DNA repair factors 53BP1, BRCA1, and MDC1. Our spatially resolved interaction maps reveal rich network intricacies, identify shared and bait-specific interaction modules, and implicate previously concealed regulators in this process...
April 7, 2018: Cell
https://www.readbyqxmd.com/read/29650893/-towards-development-of-innovative-cancer-therapies-trans-omics-approach
#10
Reika Kawabata-Iwakawa, Masahiko Nishiyama
Comprehensive genomic and transcriptome analyses using next-generation sequencing(NGS)analysis has lead a discovery of a variety of novel driver gene mutations and new therapeutic targets for cancer patients, and has remarkably improved outcome of the patients through the development novel molecular targeting drugs. Even so, in so-called intractable or refractory cancers, those "druggable"alterations common to the diseases are rarely found due to the high diversity of the tumor. Furthermore, most of molecular target therapy is known to acquire the resistance to the drug by means of multiple factors such as up-regulation of the partially inhibited pathway, mutation of the target, activation of alternative pathways, histological translocation, and oncogene de-addiction...
March 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29649654/hpv-dna-methylation-at-the-early-promoter-and-e1-e2-integrity-a-comparison-between-hpv16-hpv18-and-hpv45-in-cervical-cancer
#11
Sérgio Menezes Amaro-Filho, Cláudia Bessa Pereira Chaves, Shayany Pinto Felix, Diogo Lisbôa Basto, Liz Maria de Almeida, Miguel Angelo Martins Moreira
OBJECTIVES: To compare and describe type-specific characteristics of HPV16, HPV18 and HPV45 in cervical cancer with respect to 3'LCR methylation and disruption of E1/E2. METHODS: The methylation level of 137 cervical cancer samples (70 with HPV16, 37 with HPV18, and 30 with HPV45) of Brazilian patients was analyzed by pyrosequencing. PCR amplifications were performed to characterize E1 and E2 disruption as an episomal surrogate. RESULTS: The 3'LCR of HPV16 showed a higher methylation at all CpG sites (7%, 9%, 11%, 10% and 10%) than homologous HPV18 regions (4%, 5%...
April 9, 2018: Papillomavirus Research
https://www.readbyqxmd.com/read/29648575/early-evolutionary-divergence-between-papillary-and-anaplastic-thyroid-cancers
#12
J Capdevila, R Mayor, F F Mancuso, C Iglesias, G Caratù, I Matos, C Zafón, J Hernando, A Petit, P Nuciforo, J M Cameselle-Teijeiro, C Álvarez, J A Recio, J Tabernero, X Matias-Guiu, A Vivancos, J Seoane
Background: Papillary thyroid cancer (PTC) is the most common thyroid carcinoma and exhibits an almost uniformly good prognosis, while anaplastic thyroid cancer (ATC) is less frequent and is one of the most aggressive cancers usually resistant to conventional treatment. Current hypothesis posits that ATC derives from PTC through the progressive acquisition of a discrete number of genomic alterations and implies that the mutational landscape of ATC resembles that of PTC. However, the clinical behaviour of ATC and PTC is radically different...
April 10, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29644470/ruthenium-ii-n-alkyl-phenothiazine-complexes-as-potential-anticancer-agents
#13
Andreja Leskovac, Sandra Petrovic, Tamara Lazarevic-Pasti, Milena Krstic, Vesna Vasic
In recent years, the search for effective anticancer compounds based on transition metal complexes has been the focus of medical investigations. The synergy between the ruthenium(II) and N-alkylphenothiazine counter-ions (chlorpromazine hydrochloride, thioridazine hydrochloride and trifluoperazine dihydrochloride, respectively) through the formation of three different complexes (1-3) was investigated. We explored whether the selected counter-ions and complexes might affect redox homeostasis and genome integrity of normal human blood cells, and induce an inhibition of Na+ /K+ -ATPase and AChE at pharmacologically relevant doses...
April 11, 2018: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/29643987/proteomic-analysis-defines-kinase-taxonomies-specific-for-subtypes-of-breast-cancer
#14
Kyla A L Collins, Timothy J Stuhlmiller, Jon S Zawistowski, Michael P East, Trang T Pham, Claire R Hall, Daniel R Goulet, Samantha M Bevill, Steven P Angus, Sara H Velarde, Noah Sciaky, Tudor I Oprea, Lee M Graves, Gary L Johnson, Shawn M Gomez
Multiplexed small molecule inhibitors covalently bound to Sepharose beads (MIBs) were used to capture functional kinases in luminal, HER2-enriched and triple negative (basal-like and claudin-low) breast cancer cell lines and tumors. Kinase MIB-binding profiles at baseline without perturbation proteomically distinguished the four breast cancer subtypes. Understudied kinases, whose disease associations and pharmacology are generally unexplored, were highly represented in MIB-binding taxonomies and are integrated into signaling subnetworks with kinases that have been previously well characterized in breast cancer...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29643985/replication-incompetent-gammaretroviral-and-lentiviral-vector-based-insertional-mutagenesis-screens-identify-prostate-cancer-progression-genes
#15
Victor M Bii, Casey P Collins, Jonah D Hocum, Grant D Trobridge
Replication-incompetent gammaretroviral (γRV) and lentiviral (LV) vectors have both been used in insertional mutagenesis screens to identify cancer drivers. In this approach the vectors stably integrate in the host cell genome and induce cancers by dysregulating nearby genes. The cells that contain a retroviral vector provirus in or near a proto-oncogene or tumor suppressor are preferentially enriched in a tumor. γRV and LV vectors have different integration profiles and genotoxic potential, making them potentially complementary tools for insertional mutagenesis screens...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29643418/contextual-determinants-of-tgf%C3%AE-action-in-development-immunity-and-cancer
#16
REVIEW
Charles J David, Joan Massagué
Few cell signals match the impact of the transforming growth factor-β (TGFβ) family in metazoan biology. TGFβ cytokines regulate cell fate decisions during development, tissue homeostasis and regeneration, and are major players in tumorigenesis, fibrotic disorders, immune malfunctions and various congenital diseases. The effects of the TGFβ family are mediated by a combinatorial set of ligands and receptors and by a common set of receptor-activated mothers against decapentaplegic homologue (SMAD) transcription factors, yet the effects can differ dramatically depending on the cell type and the conditions...
April 11, 2018: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29642758/identification-of-significant-gene-signatures-and-prognostic-biomarkers-for-patients-with-cervical-cancer-by-integrated-bioinformatic-methods
#17
Xiaofang Li, Run Tian, Hugh Gao, Feng Yan, Le Ying, Yongkang Yang, Pei Yang, Yan'e Gao
Cervical cancer is the leading cause of death with gynecological malignancies. We aimed to explore the molecular mechanism of carcinogenesis and biomarkers for cervical cancer by integrated bioinformatic analysis. We employed RNA-sequencing details of 254 cervical squamous cell carcinomas and 3 normal samples from The Cancer Genome Atlas. To explore the distinct pathways, messenger RNA expression was submitted to a Gene Set Enrichment Analysis. Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction network analysis of differentially expressed genes were performed...
January 1, 2018: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29630095/pathogenicity-of-high-risk-hpv-infection-in-pseudocondyloma-of-vulvae-and-its-carcinogenicity-in-inducing-cervical-lesions
#18
P-F Song, J-Y Chen, Q He, J Wang, J Xu
OBJECTIVE: To identify high-risk human papillomavirus (HPV) infection in pseudocondyloma of vulvae (PV) and the causal relationship between high-risk HPV infection and cervical cancer. PATIENTS AND METHODS: The patients were divided into condyloma acuminatum group, PV groups and PV high-risk HPV infection group according to the clinical data and morphological features. Condyloma acuminatum group and PV group were two control groups. The exfoliated cells were detected and typed by human HPV nucleic acid typing kit...
March 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29629151/a-three-in-one-bullet-for-oesophageal-cancer-replication-fork-collapse-spindle-attachment-failure-and-enhanced-radiosensitivity-generated-by-a-ruthenium-ii-metallo-intercalator
#19
Martin R Gill, Paul J Jarman, Swagata Halder, Michael G Walker, Hiwa K Saeed, Jim A Thomas, Carl Smythe, Kristijan Ramadan, Katherine A Vallis
Substitutionally inert ruthenium(ii) polypyridyl complexes have been developed as DNA intercalating agents yet cellular DNA damage responses to this binding modality are largely unexplored. Here, we show the nuclear-targeting complex [Ru(phen)2 (tpphz)]2+ (phen = 1,10-phenanthroline, tpphz = tetrapyridophenazine) generates rapid and pronounced stalling of replication fork progression in p53-deficient human oesophageal cancer cells. In response, replication stress and double-strand break (DSB) DNA damage response (DDR) pathways are activated and cell proliferation is inhibited by growth arrest...
January 28, 2018: Chemical Science
https://www.readbyqxmd.com/read/29627078/the-roles-of-jak2-in-dna-damage-and-repair-in-the-myeloproliferative-neoplasms-opportunities-for-targeted-therapy
#20
REVIEW
Theodoros Karantanos, Alison R Moliterno
The JAK2V617F-positive myeloproliferative neoplasms (MPN) serve as an excellent model for the study of genomic instability accumulation during cancer progression. Recent studies highlight the implication of JAK2 activating mutations in the development of DNA damage via reactive oxygen species (ROS) production, replication stress induction and the accumulation of genomic instability via the increased degradation of p53 and acquisition of a "mutagenic" phenotype. The accumulation of genomic instability and acquisition of mutations in critical DNA damage repair (DDR) mediators appears to be implicated in the progression of JAK2V617F-positive MPN...
March 30, 2018: Blood Reviews
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