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Integrative genomics cancer

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https://www.readbyqxmd.com/read/28448782/amcp-partnership-forum-driving-value-and-outcomes-in-oncology
#1
(no author information available yet)
Innovation in cancer treatment has provided a wealth of recently available therapeutic agents and a healthy drug pipeline that promises to change the way we approach this disease and the lives of those affected in the years to come. However, the majority of these new agents, many of which are targeted to specific genomic features of various tumors, may challenge the health care system's ability to afford cancer care. This innovation drives the need to focus on the value of the treatments provided to patients with cancer and on methods to optimize the efficiency of the dollars we spend, in addition to the clinical value itself...
May 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28446242/activity-of-distinct-growth-factor-receptor-network-components-in-breast-tumors-uncovers-two-biologically-relevant-subtypes
#2
Mumtahena Rahman, Shelley M MacNeil, David F Jenkins, Gajendra Shrestha, Sydney R Wyatt, Jasmine A McQuerry, Stephen R Piccolo, Laura M Heiser, Joe W Gray, W Evan Johnson, Andrea H Bild
BACKGROUND: The growth factor receptor network (GFRN) plays a significant role in driving key oncogenic processes. However, assessment of global GFRN activity is challenging due to complex crosstalk among GFRN components, or pathways, and the inability to study complex signaling networks in patient tumors. Here, pathway-specific genomic signatures were used to interrogate GFRN activity in breast tumors and the consequent phenotypic impact of GRFN activity patterns. METHODS: Novel pathway signatures were generated in human primary mammary epithelial cells by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS (G12V), RAF1, BAD)...
April 26, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28445945/non-small-cell-lung-cancer-associated-microrna-expression-signature-integrated-bioinformatics-analysis-validation-and-clinical-significance
#3
Chunyu Li, Yunhong Yin, Xiao Liu, Xuejiao Xi, Weixiao Xue, Yiqing Qu
Recently, increasing studies of miRNA expression profiling has confirmed that miRNA plays an essential role in non-small cell lung cancer (NSCLC). However, inconsistent or discrepant results exist in these researches. In present study, we performed an integrative analysis of 32 miRNA profiling studies compared the differentially expressed miRNA between NSCLC tissue and non-cancerous lung tissue to identify candidate miRNAs associated with NSCLC. 7 upregulated and 10 downregulated miRNAs were identified as miRNA integrated-signature using Robust Rank Aggregation (RRA) method...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28440475/a-nine-mirna-signature-as-a-potential-diagnostic-marker-for-breast-carcinoma-an-integrated-study-of-1-110-cases
#4
Dan-Dan Xiong, Jun Lv, Kang-Lai Wei, Zhen-Bo Feng, Ji-Tian Chen, Ke-Cheng Liu, Gang Chen, Dian-Zhong Luo
Growing evidence indicates that microRNAs (miRNAs) play critical roles in the initiation and progression of breast carcinoma (BC) and are promising diagnostic biomarkers. In the present study, we aimed to identify a multi-marker miRNA pool with high diagnostic performance for BC. We collected miRNA expression profiles of BC samples and normal breast tissues from The Cancer Genome Atlas (TCGA) and screened differentially expressed miRNAs by conducting two‑sample t-tests and by calculating log2 fold-change (log2FC) ratios...
April 25, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28439991/melatonin-a-pleiotropic-molecule-that-modulates-dna-damage-response-and-repair-pathways
#5
REVIEW
Maryam Majidinia, Alireza Sadeghpour, Saeed Mehrzadi, Russel J Reiter, Nasrin Khatami, Bahman Yousefi
DNA repair is responsible for maintaining the integrity of the genome. Perturbations in the DNA repair pathways have been identified in several human cancers. Thus, compounds targeting DNA damage response (DDR) hold great promise in cancer therapy. A great deal of effort, in pursuit of new anticancer drugs, has been devoted to understanding the basic mechanisms and functions of the cellular DNA repair machinery. Melatonin, a widely-produced indoleamine in all organisms is associated with a reduced risk of cancer and has multiple regulatory roles on the different aspects of the DDR and DNA repair...
April 25, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28439535/a-murine-preclinical-syngeneic-transplantation-model-for-breast-cancer-precision-medicine
#6
Lorenzo Federico, Zechen Chong, Dong Zhang, Daniel J McGrail, Wei Zhao, Kang Jin Jeong, Christopher P Vellano, Zhenlin Ju, Mihai Gagea, Shuying Liu, Shreya Mitra, Jennifer B Dennison, Philip L Lorenzi, Robert Cardnell, Lixia Diao, Jing Wang, Yiling Lu, Lauren A Byers, Charles M Perou, Shiaw-Yih Lin, Gordon B Mills
We previously demonstrated that altered activity of lysophosphatidic acid in murine mammary glands promotes tumorigenesis. We have now established and characterized a heterogeneous collection of mouse-derived syngeneic transplants (MDSTs) as preclinical platforms for the assessment of personalized pharmacological therapies. Detailed molecular and phenotypic analyses revealed that MDSTs are the most heterogeneous group of genetically engineered mouse models (GEMMs) of breast cancer yet observed. Response of MDSTs to trametinib, a mitogen-activated protein kinase (MAPK) kinase inhibitor, correlated with RAS/MAPK signaling activity, as expected from studies in xenografts and clinical trials providing validation of the utility of the model...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28438193/pathos-a-decision-support-system-for-reporting-high-throughput-sequencing-of-cancers-in-clinical-diagnostic-laboratories
#7
Kenneth D Doig, Andrew Fellowes, Anthony H Bell, Andrei Seleznev, David Ma, Jason Ellul, Jason Li, Maria A Doyle, Ella R Thompson, Amit Kumar, Luis Lara, Ravikiran Vedururu, Gareth Reid, Thomas Conway, Anthony T Papenfuss, Stephen B Fox
BACKGROUND: The increasing affordability of DNA sequencing has allowed it to be widely deployed in pathology laboratories. However, this has exposed many issues with the analysis and reporting of variants for clinical diagnostic use. Implementing a high-throughput sequencing (NGS) clinical reporting system requires a diverse combination of capabilities, statistical methods to identify variants, global variant databases, a validated bioinformatics pipeline, an auditable laboratory workflow, reproducible clinical assays and quality control monitoring throughout...
April 24, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28437752/dna-repair-and-damage-pathways-in-breast-cancer-development-and-therapy
#8
REVIEW
Maryam Majidinia, Bahman Yousefi
DNA damage/repair constitutes several key pathways working in concert to eliminate DNA lesions and maintain genome stability and integrity. Defective components in DNA damage and repair machinery are an underlying cause for the development and progression of different types of cancers, and breast cancer is no exception. In this paper, we will briefly explain the importance of DNA damage and repair, introduce the current classification schemes for breast cancer, and review the known defects in the repair machinery that have been associated with the risk of breast cancer...
April 21, 2017: DNA Repair
https://www.readbyqxmd.com/read/28436987/genomic-consequences-of-aberrant-dna-repair-mechanisms-stratify-ovarian-cancer-histotypes
#9
Yi Kan Wang, Ali Bashashati, Michael S Anglesio, Dawn R Cochrane, Diljot S Grewal, Gavin Ha, Andrew McPherson, Hugo M Horlings, Janine Senz, Leah M Prentice, Anthony N Karnezis, Daniel Lai, Mohamed R Aniba, Allen W Zhang, Karey Shumansky, Celia Siu, Adrian Wan, Melissa K McConechy, Hector Li-Chang, Alicia Tone, Diane Provencher, Manon de Ladurantaye, Hubert Fleury, Aikou Okamoto, Satoshi Yanagida, Nozomu Yanaihara, Misato Saito, Andrew J Mungall, Richard Moore, Marco A Marra, C Blake Gilks, Anne-Marie Mes-Masson, Jessica N McAlpine, Samuel Aparicio, David G Huntsman, Sohrab P Shah
We studied the whole-genome point mutation and structural variation patterns of 133 tumors (59 high-grade serous (HGSC), 35 clear cell (CCOC), 29 endometrioid (ENOC), and 10 adult granulosa cell (GCT)) as a substrate for class discovery in ovarian cancer. Ab initio clustering of integrated point mutation and structural variation signatures identified seven subgroups both between and within histotypes. Prevalence of foldback inversions identified a prognostically significant HGSC group associated with inferior survival...
April 24, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28433800/chromosomal-alterations-and-gene-expression-changes-associated-with-the-progression-of-leukoplakia-to-advanced-gingivobuccal-cancer
#10
Priyanka G Bhosale, Simona Cristea, Srikant Ambatipudi, Rajiv S Desai, Rajiv Kumar, Asawari Patil, Shubhada Kane, Anita M Borges, Alejandro A Schäffer, Niko Beerenwinkel, Manoj B Mahimkar
We present an integrative genome-wide analysis that can be used to predict the risk of progression from leukoplakia to oral squamous cell carcinoma (OSCC) arising in the gingivobuccal complex (GBC). We find that the genomic and transcriptomic profiles of leukoplakia resemble those observed in later stages of OSCC and that several changes are associated with this progression, including amplification of 8q24.3, deletion of 8p23.2, and dysregulation of DERL3, EIF5A2, ECT2, HOXC9, HOXC13, MAL, MFAP5 and NELL2. Comparing copy number profiles of primary tumors with and without lymph-node metastasis, we identify alterations associated with metastasis, including amplifications of 3p26...
April 20, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28431273/chromosomal-instability-in-gastric-cancer-biology
#11
REVIEW
Saffiyeh Saboor Maleki, Christoph Röcken
Gastric cancer (GC) is the fifth most common cancer in the world and accounts for 7% of the total cancer incidence. The prognosis of GC is dismal in Western countries due to late diagnosis: approximately 70% of the patients die within 5 years following initial diagnosis. Recently, integrative genomic analyses led to the proposal of a molecular classification of GC into four subtypes, i.e.,microsatellite-instable, Epstein-Barr virus-positive, chromosomal-instable (CIN), and genomically stable GCs. Molecular classification of GC advances our knowledge of the biology of GC and may have implications for diagnostics and patient treatment...
April 18, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28429075/toward-personalized-management-in-bladder-cancer-the-promise-of-novel-molecular-taxonomy
#12
REVIEW
Marie-Lisa Eich, Lars Dyrskjøt, George J Netto
Empowered by the recent advances in next generation sequencing and bioinformatics technology, an unprecedented wave of integrated transcriptomic and genomic studies have impacted the field of bladder cancer. These studies not only have confirmed previously charted genetic pathways in bladder cancer development but also have led to the discovery of numerous additional crucial driver genetic alterations. As a result, a novel genomic-based taxonomy is emerging that promises to better define clinically relevant intrinsic subtypes of bladder cancer...
April 21, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28427716/xenopus-egg-extract-a-powerful-tool-to-study-genome-maintenance-mechanisms
#13
REVIEW
Wouter S Hoogenboom, Daisy Klein Douwel, Puck Knipscheer
DNA repair pathways are crucial to maintain the integrity of our genome and prevent genetic diseases such as cancer. There are many different types of DNA damage and specific DNA repair mechanisms have evolved to deal with these lesions. In addition to these repair pathways there is an extensive signaling network that regulates processes important for repair, such as cell cycle control and transcription. Despite extensive research, DNA damage repair and signaling are not fully understood. In vitro systems such as the Xenopus egg extract system, have played, and still play, an important role in deciphering the molecular details of these processes...
April 17, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28427147/brca1-controls-the-cell-division-axis-and-governs-ploidy-and-phenotype-in-human-mammary-cells
#14
Zhengcheng He, Nagarajan Kannan, Oksana Nemirovsky, Helen Chen, Marisa Connell, Brian Taylor, Jihong Jiang, Linda M Pilarski, Markus C Fleisch, Dieter Niederacher, Miguel Angel Pujana, Connie J Eaves, Christopher A Maxwell
BRCA1 deficiency may perturb the differentiation hierarchy present in the normal mammary gland and is associated with the genesis of breast cancers that are genomically unstable and typically display a basal-like transcriptome. Oriented cell division is a mechanism known to regulate cell fates and to restrict tumor formation. We now show that the cell division axis is altered following shRNA-mediated BRCA1 depletion in immortalized but non-tumorigenic, or freshly isolated normal human mammary cells with graded consequences in progeny cells that include aneuploidy, perturbation of cell polarity in spheroid cultures, and a selective loss of cells with luminal features...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426276/integrative-epigenetic-and-genetic-pan-cancer-somatic-alteration-portraits
#15
Lucas A Salas, Kevin C Johnson, Devin C Koestler, Dylan E O'Sullivan, Brock C Christensen
Genetic and epigenetic alterations are required for carcinogenesis and the mutation burden across tumor types has been investigated. Here, we investigate epigenetic alterations with a novel measure of global DNA methylation dysregulation, the methylation dysregulation index (MDI), across 14 cancer types in The Cancer Genome Atlas (TCGA) database. DNA methylation data-obtained using Illumina HumanMethylation450 BeadChip-was accessed from TCGA. We calculated the MDI in 14 tumor types (n = 5,592 tumors), using adjacent normal tissues (n = 701) from each tumor site...
April 20, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28423702/experience-with-precision-genomics-and-tumor-board-indicates-frequent-target-identification-but-barriers-to-delivery
#16
Alan H Bryce, Jan B Egan, Mitesh J Borad, A Keith Stewart, Grzegorz S Nowakowski, Asher Chanan-Khan, Mrinal M Patnaik, Stephen M Ansell, Michaela S Banck, Steven I Robinson, Aaron S Mansfield, Eric W Klee, Gavin R Oliver, Jennifer B McCormick, Norine E Huneke, Colleen M Tagtow, Robert B Jenkins, Kandelaria M Rumilla, Sarah E Kerr, Jean-Pierre A Kocher, Scott A Beck, Martin E Fernandez-Zapico, Gianrico Farrugia, Konstantinos N Lazaridis, Robert R McWilliams
BACKGROUND: The ability to analyze the genomics of malignancies has opened up new possibilities for off-label targeted therapy in cancers that are refractory to standard therapy. At Mayo Clinic these efforts are organized through the Center for Individualized Medicine (CIM). RESULTS: Prior to GTB, datasets were analyzed and integrated by a team of bioinformaticians and cancer biologists. Therapeutically actionable mutations were identified in 65% (92/141) of the patients tested with 32% (29/92) receiving genomically targeted therapy with FDA approved drugs or in an independent clinical trial with 45% (13/29) responding...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423598/next-generation-mapping-reveals-novel-large-genomic-rearrangements-in-prostate-cancer
#17
Weerachai Jaratlerdsiri, Eva K F Chan, Desiree C Petersen, Claire Yang, Peter I Croucher, M S Riana Bornman, Palak Sheth, Vanessa M Hayes
Complex genomic rearrangements are common molecular events driving prostate carcinogenesis. Clinical significance, however, has yet to be fully elucidated. Detecting the full range and subtypes of large structural variants (SVs), greater than one kilobase in length, is challenging using clinically feasible next generation sequencing (NGS) technologies. Next generation mapping (NGM) is a new technology that allows for the interrogation of megabase length DNA molecules outside the detection range of single-base resolution NGS...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420414/integrated-genomic-analysis-of-mitochondrial-rna-processing-in-human-cancers
#18
Youssef Idaghdour, Alan Hodgkinson
BACKGROUND: The mitochondrial genome is transcribed as continuous polycistrons of RNA containing multiple genes. As a consequence, post-transcriptional events are critical for the regulation of gene expression and therefore all aspects of mitochondrial function. One particularly important process is the m(1)A/m(1)G RNA methylation of the ninth position of different mitochondrial tRNAs, which allows efficient processing of mitochondrial mRNAs and protein translation, and de-regulation of genes involved in these processes has been associated with altered mitochondrial function...
April 18, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28418844/loss-of-tumour-specific-atm-protein-expression-is-an-independent-prognostic-factor-in-early-resected-nsclc
#19
Lars F Petersen, Alexander C Klimowicz, Shannon Otsuka, Anifat A Elegbede, Stephanie K Petrillo, Tyler Williamson, Chris T Williamson, Mie Konno, Susan P Lees-Miller, Desiree Hao, Don Morris, Anthony M Magliocco, D Gwyn Bebb
Ataxia-telangiectasia mutated (ATM) is critical in maintaining genomic integrity. In response to DNA double-strand breaks, ATM phosphorylates downstream proteins involved in cell-cycle checkpoint arrest, DNA repair, and apoptosis. Here we investigate the frequency, and influence of ATM deficiency on outcome, in early-resected non-small cell lung cancer (NSCLC). Tissue microarrays, containing 165 formalin-fixed, paraffin-embedded resected NSCLC tumours from patients diagnosed at the Tom Baker Cancer Centre, Calgary, Canada, between 2003 and 2006, were analyzed for ATM expression using quantitative fluorescence immunohistochemistry...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417933/radiogenomic-analysis-of-oncological-data-a-technical-survey
#20
REVIEW
Mariarosaria Incoronato, Marco Aiello, Teresa Infante, Carlo Cavaliere, Anna Maria Grimaldi, Peppino Mirabelli, Serena Monti, Marco Salvatore
In the last few years, biomedical research has been boosted by the technological development of analytical instrumentation generating a large volume of data. Such information has increased in complexity from basic (i.e., blood samples) to extensive sets encompassing many aspects of a subject phenotype, and now rapidly extending into genetic and, more recently, radiomic information. Radiogenomics integrates both aspects, investigating the relationship between imaging features and gene expression. From a methodological point of view, radiogenomics takes advantage of non-conventional data analysis techniques that reveal meaningful information for decision-support in cancer diagnosis and treatment...
April 12, 2017: International Journal of Molecular Sciences
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