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https://www.readbyqxmd.com/read/29780850/canada-wide-epidemic-of-emm74-group-a-streptococcus-invasive-disease
#1
Sarah Teatero, Allison McGeer, Gregory J Tyrrell, Linda Hoang, Hanan Smadi, Marc-Christian Domingo, Paul N Levett, Michael Finkelstein, Ken Dewar, Agron Plevneshi, Taryn B T Athey, Jonathan B Gubbay, Michael R Mulvey, Irene Martin, Walter Demczuk, Nahuel Fittipaldi
Background: The number of invasive group A Streptococcus (iGAS) infections due to hitherto extremely rare type emm74 strains has increased in several Canadian provinces since late 2015. We hypothesized that the cases recorded in the different provinces are linked and caused by strains of an emm74 clone that recently emerged and expanded explosively. Methods: We analyzed both active and passive surveillance data for iGAS infections and used whole-genome sequencing to investigate the phylogenetic relationships of the emm74 strains responsible for these invasive infections country-wide...
May 2018: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/29779219/immunohistochemical-and-molecular-analysis-of-spitzoid-neoplasms-with-pulverocyte-subclones
#2
S M Amin, A M Haugh, J A Bubley, A E Verzì, E A Merkel, C Y Lee, V L Quan, E M Garfield, L M Sholl, B Zhang, P Gerami
BACKGROUND: Clonal naevi are characterized by a focal proliferation of pigmented melanocytes in an otherwise banal naevus. These subclones are often composed of aggregates of larger, epithelioid melanocytes with nuclear atypia and dusty-grey cytoplasmic pigmentation, which are referred to as 'pulverocytes', and this finding may lead to a misdiagnosis of malignant melanoma (MM). AIM: To characterize the significance of subclones of dusty-grey pigmented epithelioid melanocytes within spitzoid neoplasms...
May 20, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29778230/etv6-runx1-positive-childhood-acute-lymphoblastic-leukemia-all-the-spectrum-of-clonal-heterogeneity-and-its-impact-on-prognosis
#3
Μ Αmpatzidou, S I Papadhimitriou, G Paterakis, D Pavlidis, Κ Tsitsikas, I V Kostopoulos, V Papadakis, G Vassilopoulos, S Polychronopoulou
The prognostic significance of the ETV6/RUNX1-fusion and of the accompanying aberrations is disputable; whether co-existing sub-clones are responsible for delayed MRD-clearance and thus, moderate outcome, remains to be clarified. We studied, in a paediatric cohort of 119 B-ALLs, the relation between the ETV6/RUNX1 aberration and the co-existing subclones with (a) presenting clinical/biological features, (b) early response to treatment(MRD) and (c) long-term outcome over a 12-year period. Patients were homogeneously treated according to BFM-based-protocols...
August 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29776953/the-landscape-of-actionable-genomic-alterations-in-cell-free-circulating-tumor-dna-from-21-807-advanced-cancer-patients
#4
Oliver A Zill, Kimberly C Banks, Stephen R Fairclough, Stefanie Mortimer, James V Vowles, Reza Mokhtari, David R Gandara, Philip C Mack, Justin I Odegaard, Rebecca J Nagy, Arthur M Baca, Helmy Eltoukhy, Darya I Chudova, Richard B Lanman, AmirAli Talasaz
PURPOSE: Cell-free DNA (cfDNA) sequencing provides a non-invasive method for obtaining actionable genomic information to guide personalized cancer treatment, but the presence of multiple alterations in circulation related to treatment and tumor heterogeneity complicate the interpretation of the observed variants. Experimental Design: We describe the somatic mutation landscape of 70 cancer genes from cfDNA deep-sequencing analysis of 21,807 patients with treated, late-stage cancers across >50 cancer types...
May 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29776924/tools-for-rapid-genetic-engineering-of-vibrio-fischeri
#5
Karen L Visick, Kelsey M Hodge-Hanson, Alice H Tischler, Allison K Bennett, Vincent Mastrodomenico
Vibrio fischeri is used as a model for number of processes, including symbiosis, quorum sensing, bioluminescence, and biofilm formation. Many of these studies depend on generating deletion mutants and complementing them. Engineering such strains, however, is a time-consuming, multi-step process that relies on cloning and subcloning. Here, we describe a set of tools that can be used to rapidly engineer deletions and insertions in the V. fischeri chromosome without cloning. We developed a uniform approach for generating deletions using PCR SOEing (Splicing by Overlap Extension) with antibiotic cassettes flanked by standardized linker sequences...
May 18, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29775627/acquisition-of-tumorigenic-potential-and-therapeutic-resistance-in-cd133-subpopulation-of-prostate-cancer-cells-exhibiting-stem-cell-like-characteristics
#6
Rajnee Kanwal, Sanjeev Shukla, Ethan Walker, Sanjay Gupta
The role of CD133 (Prominin-1) as a cancer stem cell marker may be useful for therapeutic approaches and prognostication in prostate cancer patients. We investigated the stem-cell-related function and biological features of a subpopulation of CD133+ cells isolated from established primary human prostate cancer cell lines. The CD133+ cells sorted from human prostate cancer 22Rv1 exhibited high clonogenic and tumorigenic capabilities, sphere forming capacity and serially reinitiated transplantable tumors in NOD-SCID mice...
May 15, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29771315/palimpsest-an-r-package-for-studying-mutational-and-structural-variant-signatures-along-clonal-evolution-in-cancer
#7
Jayendra Shinde, Quentin Bayard, Sandrine Imbeaud, Théo Z Hirsch, Feng Liu, Victor Renault, Jessica Zucman-Rossi, Eric Letouzé
Summary: Cancer genomes are altered by various mutational processes and, like palimpsests, bear the signatures of these different processes. The Palimpsest R package provides a complete workflow for the characterization and visualization of mutational signatures and their evolution along tumor development. The package covers a wide range of functions for extracting both base substitution and structural variant signatures, inferring the clonality of each alteration and analyzing the evolution of mutational processes between early clonal and late subclonal events...
May 16, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29770657/-cloning-expression-and-immunity-analysis-of-transketolase-of-echinococcus-granulosus
#8
Cao De-Ping, Zhang Yao-Gang, Li Chao-Qun, Liu Jia, Jiang Bo-Fan
OBJECTIVE: To obtain the prokaryotic expression of transketolase genes and analyze its value as a diagnostic antigen for echinococcosis. METHODS: TK gene was amplified by PCR and cloned into prokaryotic vector pMD19-EgTK, and then subcloned into the expression vector pET-28a. The target gene TK prokaryotic expression plasmid pET-28a was constructed and transferred into BL21. The purified protein was identified by SDS-PAGE and Western blotting. The blood samples of patients with cystic echinococcosis (CE group), alveolar echinococcosis (AE group) and healthy people (healthy group) were collected and detected by ELISA with the recombinant EgTK protein as a diagnostic antigen...
April 20, 2018: Zhongguo Xue Xi Chong Bing Fang Zhi za Zhi, Chinese Journal of Schistosomiasis Control
https://www.readbyqxmd.com/read/29760223/genomic-heterogeneity-and-the-small-renal-mass
#9
Daiki Ueno, Zuoquan Xie, Marta Boeke, Jamil Syed, Kevin A Nguyen, Patrick McGillivray, Adebowale Adeniran, Peter A Humphrey, Garrett M Dancik, Yuval Kluger, Zongzhi Liu, Harriet M Kluger, Brian Shuch
PURPOSE: Tumor heterogeneity may represent a barrier to pre-operative genomic characterization by needle biopsy in clear cell renal cell carcinoma (ccRCC). The extent of heterogeneity in small renal tumors remains unknown. Therefore, we set out to evaluate heterogeneity in resected large and small renal tumors. EXPERIMENTAL DESIGN: We conducted a study from 2013 through 2016, that evaluated 47 consecutive ccRCC tumors resected during radical or partial nephrectomy...
May 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29753709/production-of-polyclonal-antibodies-for-capsicum-chlorosis-virus-cacv-infecting-chilli-in-india-through-recombinant-nucleocapsid-protein-expression-and-its-application
#10
B D Haokip, D Alice, R Selvarajan, K Nagendran, L Rajendran, S K Manoranjitham, G Karthikeyan
Bud necrosis and chlorotic spots causing virus affecting chilli crop in Tamil Nadu (India) was identified as Capsicum chlorosis virus (CaCV). Specific primers were used for amplification and sequencing of the nucleocapsid protein (NP) gene. Polyclonal antibody against the bacterially expressed NP from the CaCV-TN-CBE isolate was produced using recombinant DNA technology. NP gene was subcloned into the pET-28a (+) vector and expressed by transformation in BL21 (DE3) pLysS. The expressed protein was about ~34 kDa and was confirmed through western blot analysis using Groundnut bud necrosis virus (GBNV) polyclonal antiserum from ICRISAT, India...
May 10, 2018: Journal of Virological Methods
https://www.readbyqxmd.com/read/29749397/recurrent-somatic-mutations-are-rare-in-patients-with-cryptic-dyskeratosis-congenita
#11
Martin Kirschner, Angela Maurer, Marcin W Wlodarski, Monica S Ventura Ferreira, Anne-Sophie Bouillon, Insa Halfmeyer, Wolfgang Blau, Michael Kreuter, Martin Rosewich, Selim Corbacioglu, Joachim Beck, Michaela Schwarz, Jörg Bittenbring, Markus P Radsak, Christian Matthias Wilk, Steffen Koschmieder, Matthias Begemann, Ingo Kurth, Mirle Schemionek, Tim H Brümmendorf, Fabian Beier
Dyskeratosis congenita (DKC) is a paradigmatic telomere disorder characterized by substantial and premature telomere shortening, bone marrow failure, and a dramatically increased risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). DKC can occur as a late-onset, so-called cryptic form, with first manifestation in adults. Somatic MDS-related mutations are found in up to 35% of patients with acquired aplastic anemia (AA), especially in patients with short telomeres. The aim of our study was to investigate whether cryptic DKC is associated with an increased incidence of MDS-related somatic mutations, thereby linking the accelerated telomere shortening with the increased risk of MDS/AML...
April 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29748622/genomic-features-of-renal-cell-carcinoma-with-venous-tumor-thrombus
#12
Gregor Warsow, Daniel Hübschmann, Kortine Kleinheinz, Cathleen Nientiedt, Martina Heller, Laura Van Coile, Yanis Tolstov, Lukas Trennheuser, Kathrin Wieczorek, Carine Pecqueux, Claudia Gasch, Timur Kuru, Joanne Nyarangi-Dix, Gencay Hatiboglu, Dogu Teber, Sven Perner, Albrecht Stenzinger, Wilfried Roth, Boris Hadaschik, Sascha Pahernik, Dirk Jäger, Carsten Grüllich, Anette Duensing, Roland Eils, Matthias Schlesner, Holger Sültmann, Markus Hohenfellner, Stefan Duensing
A venous tumor thrombus (VTT) is a potentially lethal complication of renal cell carcinoma (RCC) but virtually nothing is known about the underlying natural history. Based on our observation that venous thrombi contain significant numbers of viable tumor cells, we applied multiregion whole exome sequencing to a total of 37 primary tumor and VTT samples including normal tissue specimens from five consecutive patients. Our findings demonstrate mutational heterogeneity between primary tumor and VTT with 106 of 483 genes (22%) harboring functional SNVs and/or indels altered in either primary tumor or thrombus...
May 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29746849/characterisation-of-re-entrant-circuit-or-rotational-activity-in-vitro-using-the-hl1-6-myocyte-cell-line
#13
Charles Houston, Konstantinos N Tzortzis, Caroline Roney, Andrea Saglietto, David S Pitcher, Chris Cantwell, Rasheda A Chowdhury, Fu Siong Ng, Nicholas S Peters, Emmanuel Dupont
Fibrillation is the most common arrhythmia observed in clinical practice. Understanding of the mechanisms underlying its initiation and maintenance remains incomplete. Functional re-entries are potential drivers of the arrhythmia. Two main concepts are still debated, the "leading circle" and the "spiral wave or rotor" theories. The homogeneous subclone of the HL1 atrial-derived cardiomyocyte cell line, HL1-6, spontaneously exhibits re-entry on a microscopic scale due to its slow conduction velocity and the presence of triggers, making it possible to examine re-entry at the cellular level...
May 7, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29746265/microenvironment-signaling-driving-lymphomagenesis
#14
Léa Verdière, Frédéric Mourcin, Karin Tarte
PURPOSE OF REVIEW: In addition to the recent progresses in the description of the genetic landscape of B-cell non-Hodgkin's lymphomas, tumor microenvironment has progressively emerged as a central determinant of early lymphomagenesis, subclonal evolution, drug resistance, and late progression/transformation. The purpose of this review is to outline the most recent findings regarding malignant B-cell niche composition and organization supporting direct and indirect tumor-promoting functions of lymphoma microenvironment...
May 8, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29740169/gain-of-function-mutations-in-dnmt3a-in-patients-with-paraganglioma
#15
Laura Remacha, Maria Currás-Freixes, Raúl Torres-Ruiz, Francesca Schiavi, Rafael Torres-Pérez, Bruna Calsina, Rocío Letón, Iñaki Comino-Méndez, Juan M Roldán-Romero, Cristina Montero-Conde, María Santos, Lucía Inglada Pérez, Guillermo Pita, María R Alonso, Emiliano Honrado, Susana Pedrinaci, Benedicto Crespo-Facorro, Antonio Percesepe, Maurizio Falcioni, Sandra Rodríguez-Perales, Esther Korpershoek, Santiago Ramón-Maiques, Giuseppe Opocher, Cristina Rodríguez-Antona, Mercedes Robledo, Alberto Cascón
PURPOSE: The high percentage of patients carrying germline mutations makes pheochromocytomas/paragangliomas the most heritable of all tumors. However, there are still cases unexplained by mutations in the known genes. We aimed to identify the genetic cause of disease in patients strongly suspected of having hereditary tumors. METHODS: Whole-exome sequencing was applied to the germlines of a parent-proband trio. Genome-wide methylome analysis, RNA-seq, CRISPR/Cas9 gene editing, and targeted sequencing were also performed...
May 8, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29738763/3d-culture-system-containing-gellan-gum-restores-oncogene-dependence-in-ros1-rearrangements-non-small-cell-lung-cancer
#16
Bo Gong, Tomoko Oh-Hara, Naoya Fujita, Ryohei Katayama
The ROS1 fusion gene has been identified in approximately 1% of non-small cell lung cancer (NSCLC) cases. Several clinical studies have highlighted ROS1 as a promising therapeutic target because crizotinib, a multi-targeted drug against ROS1, ALK, and the MET proto-oncogene, has elicited remarkable responses in ROS1-rearrangements NSCLC. However, acquired resistance mediated by ROS1 kinase domain mutations has been identified and a system to assess ROS1 inhibitors for these resistant mutations is necessary for the promotion of drug development...
May 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29732315/notch1-is-aberrantly-activated-in-chronic-lymphocytic-leukemia-hematopoietic-stem-cells
#17
Mauro Di Ianni, Stefano Baldoni, Beatrice Del Papa, Patrizia Aureli, Erica Dorillo, Filomena De Falco, Elisa Albi, Emanuela Varasano, Ambra Di Tommaso, Raffaella Giancola, Patrizia Accorsi, Gianluca Rotta, Chiara Rompietti, Estevão Carlos Silva Barcelos, Antonio Francesco Campese, Paolo Di Bartolomeo, Isabella Screpanti, Emanuela Rosati, Franca Falzetti, Paolo Sportoletti
To investigate chronic lymphocytic leukemia (CLL)-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs). In NOTCH1- mutated CLL, we detected subclonal mutations in 57% CD34+/CD38- HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an increased mutational burden compared to HSCs. Flow cytometric analysis revealed significantly higher NOTCH1 activation in CD34+/CD38- and CD34+/CD38+ cells from CLL patients, regardless NOTCH1 mutation compared to healthy donors...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29721644/morphology-oriented-epigenetic-research
#18
REVIEW
Sohei Kitazawa, Ryuma Haraguchi, Riko Kitazawa
Cytosine methylation plays a major role in the regulation of sequential and tissue-specific expression of genes. De novo aberrant DNA methylation and demethylation are also crucial processes in tumorigenesis and tumor progression. The mechanisms of how and when such aberrant methylation and demethylation occur in tumor cells are still obscure, however. To evaluate subtle epigenetic alteration among minor subclonal populations, morphology-oriented epigenetic analysis is requisite, especially where heterogeneity and flexibility are as notable as in the process of cancer progression and cellular differentiation at critical stages...
May 2, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29720620/plasmepsin-ii-iii-copy-number-accounts-for-bimodal-piperaquine-resistance-among-cambodian-plasmodium-falciparum
#19
Selina Bopp, Pamela Magistrado, Wesley Wong, Stephen F Schaffner, Angana Mukherjee, Pharath Lim, Mehul Dhorda, Chanaki Amaratunga, Charles J Woodrow, Elizabeth A Ashley, Nicholas J White, Arjen M Dondorp, Rick M Fairhurst, Frederic Ariey, Didier Menard, Dyann F Wirth, Sarah K Volkman
Multidrug resistant Plasmodium falciparum in Southeast Asia endangers regional malaria elimination and threatens to spread to other malaria endemic areas. Understanding mechanisms of piperaquine (PPQ) resistance is crucial for tracking its emergence and spread, and to develop effective strategies for overcoming it. Here we analyze a mechanism of PPQ resistance in Cambodian parasites. Isolates exhibit a bimodal dose-response curve when exposed to PPQ, with the area under the curve quantifying their survival in vitro...
May 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29720585/de-novo-activating-mutations-drive-clonal-evolution-and-enhance-clonal-fitness-in-kmt2a-rearranged-leukemia
#20
Axel Hyrenius-Wittsten, Mattias Pilheden, Helena Sturesson, Jenny Hansson, Michael P Walsh, Guangchun Song, Julhash U Kazi, Jian Liu, Ramprasad Ramakrishan, Cristian Garcia-Ruiz, Stephanie Nance, Pankaj Gupta, Jinghui Zhang, Lars Rönnstrand, Anne Hultquist, James R Downing, Karin Lindkvist-Petersson, Kajsa Paulsson, Marcus Järås, Tanja A Gruber, Jing Ma, Anna K Hagström-Andersson
Activating signaling mutations are common in acute leukemia with KMT2A (previously MLL) rearrangements (KMT2A-R). These mutations are often subclonal and their biological impact remains unclear. Using a retroviral acute myeloid mouse leukemia model, we demonstrate that FLT3 ITD , FLT3 N676K , and NRAS G12D accelerate KMT2A-MLLT3 leukemia onset. Further, also subclonal FLT3 N676K mutations accelerate disease, possibly by providing stimulatory factors. Herein, we show that one such factor, MIF, promotes survival of mouse KMT2A-MLLT3 leukemia initiating cells...
May 2, 2018: Nature Communications
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