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Clonal evolution

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https://www.readbyqxmd.com/read/28429724/clonal-evolution-in-myelodysplastic-syndromes
#1
Pedro da Silva-Coelho, Leonie I Kroeze, Kenichi Yoshida, Theresia N Koorenhof-Scheele, Ruth Knops, Louis T van de Locht, Aniek O de Graaf, Marion Massop, Sarah Sandmann, Martin Dugas, Marian J Stevens-Kroef, Jaroslav Cermak, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Theo de Witte, Nicole M A Blijlevens, Petra Muus, Gerwin Huls, Bert A van der Reijden, Seishi Ogawa, Joop H Jansen
Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5-11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28428775/genomics-reveals-a-unique-clone-of-burkholderia-cenocepacia-harboring-an-actively-excising-novel-genomic-island
#2
Prashant P Patil, Swapna Mali, Samriti Midha, Vikas Gautam, Lona Dash, Sunil Kumar, Jayanthi Shastri, Lipika Singhal, Prabhu B Patil
Burkholderia cenocepacia is a clinically dominant form among the other virulent species of Burkholderia cepacia complex (Bcc). In the present study, we sequenced and analyzed the genomes of seven nosocomial Bcc isolates, five of which were isolated from the bloodstream infections and two isolates were recovered from the hospital setting during the surveillance. Genome-based species identification of the Bcc isolates using a type strain explicitly identified the species as B. cenocepacia. Moreover, single nucleotide polymorphism analysis revealed that the six isolates were clonal and phylogenetically distinct from the other B...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28423542/dna-methylation-intratumor-heterogeneity-in-localized-lung-adenocarcinomas
#3
Kelly Quek, Jun Li, Marcos Estecio, Jiexin Zhang, Junya Fujimoto, Emily Roarty, Latasha Little, Chi-Wan Chow, Xingzhi Song, Carmen Behrens, Taiping Chen, William N William, Stephen Swisher, John Heymach, Ignacio Wistuba, Jianhua Zhang, Andrew Futreal, Jianjun Zhang
Cancers are composed of cells with distinct molecular and phenotypic features within a given tumor, a phenomenon termed intratumor heterogeneity (ITH). Previously, we have demonstrated genomic ITH in localized lung adenocarcinomas; however, the nature of methylation ITH in lung cancers has not been well investigated. In this study, we generated methylation profiles of 48 spatially separated tumor regions from 11 localized lung adenocarcinomas and their matched normal lung tissues using Illumina Infinium Human Methylation 450K BeadChip array...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423296/eltrombopag-added-to-standard-immunosuppression-for-aplastic-anemia
#4
Danielle M Townsley, Phillip Scheinberg, Thomas Winkler, Ronan Desmond, Bogdan Dumitriu, Olga Rios, Barbara Weinstein, Janet Valdez, Jennifer Lotter, Xingmin Feng, Marie Desierto, Harshraj Leuva, Margaret Bevans, Colin Wu, Andre Larochelle, Katherine R Calvo, Cynthia E Dunbar, Neal S Young
Background Acquired aplastic anemia results from immune-mediated destruction of bone marrow. Immunosuppressive therapies are effective, but reduced numbers of residual stem cells may limit their efficacy. In patients with aplastic anemia that was refractory to immunosuppression, eltrombopag, a synthetic thrombopoietin-receptor agonist, led to clinically significant increases in blood counts in almost half the patients. We combined standard immunosuppressive therapy with eltrombopag in previously untreated patients with severe aplastic anemia...
April 20, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28417598/genetic-analysis-of-a-morphologically-heterogeneous-ovarian-endometrioid-carcinoma
#5
Felipe C Geyer, Fresia Pareja, Kathleen A Burke, Anne M Schultheis, Yaser R Hussein, Jiqing Ye, Maria R De Filippo, Caterina Marchio, Gabriel S Macedo, Salvatore Piscuoglio, Raymond S Lim, Eugene Toy, Rajmohan Murali, Achim A Jungbluth, Jorge S Reis-Filho, Robert A Soslow, Britta Weigelt
AIMS: Low-grade ovarian endometrioid carcinomas may be associated with high-grade components. Whether the latter are clonally-related to and originate from the low-grade endometrioid carcinoma remains unclear. Here we employed massively parallel sequencing to characterize the genomic landscape and clonal relatedness of an ovarian endometrioid carcinoma containing low- and high-grade components. METHODS AND RESULTS: DNA samples extracted from each tumor component (low-grade endometrioid, high-grade anaplastic, high-grade squamous) and matched normal tissue were subjected to targeted massively parallel sequencing using the 410 gene Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing assay...
April 18, 2017: Histopathology
https://www.readbyqxmd.com/read/28416802/rna-editing-dependent-epitranscriptome-diversity-in-cancer-stem-cells
#6
REVIEW
Qingfei Jiang, Leslie A Crews, Frida Holm, Catriona H M Jamieson
Cancer stem cells (CSCs) can regenerate all facets of a tumour as a result of their stem cell-like capacity to self-renew, survive and become dormant in protective microenvironments. CSCs evolve during tumour progression in a manner that conforms to Charles Darwin's principle of natural selection. Although somatic DNA mutations and epigenetic alterations promote evolution, post-transcriptional RNA modifications together with RNA binding protein activity (the 'epitranscriptome') might also contribute to clonal evolution through dynamic determination of RNA function and gene expression diversity in response to environmental stimuli...
April 18, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28415744/emt-like-circulating-tumor-cells-in-ovarian-cancer-patients-are-enriched-by-platinum-based-chemotherapy
#7
Issam Chebouti, Sabine Kasimir-Bauer, Paul Buderath, Pauline Wimberger, Siegfried Hauch, Rainer Kimmig, Jan Dominik Kuhlmann
BACKGROUND: Assuming that tumor cell dissemination requires a shift to a mesenchymal phenotype, we analyzed the incidence of epithelial-to-mesenchymal-transition (EMT)-like circulating tumor cells (CTCs) in ovarian cancer patients and inquired, how their molecular phenotypes respond to platinum-based chemotherapy and influence outcome. RESULTS: Before surgery, overall detection rate for epithelial CTCs was 18%. EMT-like CTCs were more frequently observed (30%) and were mutually exclusive to epithelial CTCs in the majority of patients (82%)...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412384/molecular-epidemiology-of-penicillinase-producing-neisseria-gonorrhoeae-isolates-in-france
#8
Maité Micaëlo, Agathe Goubard, Guy La Ruche, Erick Denamur, Olivier Tenaillon, Emmanuelle Cambau, Hervé Jacquier, Béatrice Bercot
OBJECTIVES: Characterising the molecular epidemiology of antibiotic resistance is crucial for a better understanding of the evolution and spread of resistance in Neisseria gonorrhoeae. Here, we examine the molecular epidemiology of penicillinase-producing N. gonorrhoeae (PPNG) isolates in France. METHODS: We investigated 176 PPNG isolates collected between 2010 and 2012 by the National Reference Centre in France. Genotyping was performed using the NG-MAST technique, blaTEM genes were Sanger-sequenced, and plasmids were characterized by PCR-typing...
April 13, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28405930/single-cell-sequencing-and-tumorigenesis-improved-understanding-of-tumor-evolution-and-metastasis
#9
REVIEW
Darrell L Ellsworth, Heather L Blackburn, Craig D Shriver, Shahrooz Rabizadeh, Patrick Soon-Shiong, Rachel E Ellsworth
Extensive genomic and transcriptomic heterogeneity in human cancer often negatively impacts treatment efficacy and survival, thus posing a significant ongoing challenge for modern treatment regimens. State-of-the-art DNA- and RNA-sequencing methods now provide high-resolution genomic and gene expression portraits of individual cells, facilitating the study of complex molecular heterogeneity in cancer. Important developments in single-cell sequencing (SCS) technologies over the past 5 years provide numerous advantages over traditional sequencing methods for understanding the complexity of carcinogenesis, but significant hurdles must be overcome before SCS can be clinically useful...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28402390/hybridization-drives-evolution-of-apomicts-in-rubus-subgenus-rubus-evidence-from-microsatellite-markers
#10
Petra Šarhanová, Timothy F Sharbel, Michal Sochor, Radim J Vašut, Martin Dancák, Bohumil Trávnícek
Background and Aims: Rubus subgenus Rubus is a group of mostly apomictic and polyploid species with a complicated taxonomy and history of ongoing hybridization. The only polyploid series with prevailing sexuality is the series Glandulosi , although the apomictic series Discolores and Radula also retain a high degree of sexuality, which is influenced by environmental conditions and/or pollen donors. The aim of this study is to detect sources of genetic variability, determine the origin of apomictic taxa and validate microsatellite markers by cloning and sequencing...
April 11, 2017: Annals of Botany
https://www.readbyqxmd.com/read/28400427/circulating-dna-demonstrates-convergent-evolution-and-common-resistance-mechanisms-during-treatment-of-colorectal-cancer
#11
Alain R Thierry, Brice Pastor, Zhi-Qin Jiang, Anastasia Katsiampoura, Christine Parseghian, Jonathan M Loree, Michael J Overman, Cynthia Sanchez, Safia El Messaoudi, Marc Ychou, Scott Kopetz
Purpose: Liquid biopsies allow the tracking of clonal dynamics and detection of mutations during treatment. <p>Experimental design: We evaluated under blinded conditions the ability of cell free DNA (cfDNA) to detect RAS/BRAF mutations in the plasma of 42 metastatic colorectal cancer patients treated on a phase Ib/II trial of FOLFOX and dasatinib, with or without cetuximab. Results: Prior to treatment, sequencing of archival tissue detected mutations in 25/42 patients (60%), while the cfDNA assay detected mutations in 37/42 patients (88%)...
April 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28396495/clonal-selection-and-asymmetric-distribution-of-human-leukemia-in-murine-xenografts-revealed-by-cellular-barcoding
#12
Mirjam E Belderbos, Taco Koster, Bertien Ausema, Sabrina Jacobs, Sharlaine Sowdagar, Erik Zwart, Eveline de Bont, Gerald de Haan, Leonid V Bystrykh
Genetic and phenotypic heterogeneity of human leukemia is thought to drive leukemia progression through a Darwinian process of selection and evolution of increasingly malignant clones. However, the lack of markers to uniquely identify individual leukemia clones precludes high resolution tracing of their clonal dynamics. Here, we employ cellular barcoding to analyze the clonal behavior of patient-derived leukemia-propagating cells (LPCs) in murine xenografts. Using a leukemic cell line and diagnostic bone marrow cells from six patients with B-progenitor cell acute lymphoblastic leukemia (B-ALL), we demonstrate that patient-derived xenografts were highly polyclonal, consisting of tens to hundreds of LPC clones...
April 10, 2017: Blood
https://www.readbyqxmd.com/read/28395056/what-is-the-clinical-utility-of-repeat-snp-array-testing-in-the-follow-up-of-myeloid-neoplasms-a-retrospective-analysis-of-44-patients-with-serial-snp-arrays
#13
Basma Basha, Janice Smith, Heesun J Rogers, James R Cook
Objectives: Single-nucleotide polymorphism (SNP) arrays have been shown to identify cytogenetic abnormalities in myeloid neoplasms that may be missed by metaphase cytogenetics alone at initial diagnosis. This study examines the utility of serial SNP arrays in follow-up testing of myeloid neoplasms. Methods: We retrospectively reviewed results of SNP array testing in 44 patients with myeloid neoplasms and more than one SNP array study (n = 133 SNP arrays total; median, three per patient; range, two to eight per patient)...
March 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28380360/the-mutational-landscape-of-circulating-tumor-cells-in-multiple-myeloma
#14
Yuji Mishima, Bruno Paiva, Jiantao Shi, Jihye Park, Salomon Manier, Satoshi Takagi, Mira Massoud, Adriana Perilla-Glen, Yosra Aljawai, Daisy Huynh, Aldo M Roccaro, Antonio Sacco, Marzia Capelletti, Alexandre Detappe, Diego Alignani, Kenneth C Anderson, Nikhil C Munshi, Felipe Prosper, Jens G Lohr, Gavin Ha, Samuel S Freeman, Eliezer M Van Allen, Viktor A Adalsteinsson, Franziska Michor, Jesus F San Miguel, Irene M Ghobrial
The development of sensitive and non-invasive "liquid biopsies" presents new opportunities for longitudinal monitoring of tumor dissemination and clonal evolution. The number of circulating tumor cells (CTCs) is prognostic in multiple myeloma (MM), but there is little information on their genetic features. Here, we have analyzed the genomic landscape of CTCs from 29 MM patients, including eight cases with matched/paired bone marrow (BM) tumor cells. Our results show that 100% of clonal mutations in patient BM were detected in CTCs and that 99% of clonal mutations in CTCs were present in BM MM...
April 4, 2017: Cell Reports
https://www.readbyqxmd.com/read/28378425/follicular-lymphoma-state-of-the-art-icml-workshop-in-lugano-2015
#15
REVIEW
Randy D Gascoyne, Bertrand Nadel, Laura Pasqualucci, Jude Fitzgibbon, Jacqueline E Payton, Ari Melnick, Oliver Weigert, Karin Tarte, John G Gribben, Jonathan W Friedberg, John F Seymour, Franco Cavalli, Emanuele Zucca
The 13th International Conference on Malignant Lymphoma held in Lugano in June 2015 was preceded by a closed workshop (organized in collaboration with the American Association for Cancer Research and the European School of Oncology) with the aim of developing an up-to-date understanding of the biology of follicular lymphoma and the clinical implications of new findings in the field. Discussed topics included the mutational spectrum at diagnosis, the clinical correlates of genetic and epigenetic alterations, the mechanisms of clonal evolution and histological transformation, the cross talk between tumor cells and microenvironment, and the development of novel treatments...
April 4, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28378367/clonal-evolution-detected-with-conventional-cytogenetic-analysis-is-a-potent-prognostic-factor-in-adult-patients-with-relapsed-aml
#16
Hiroaki Shimizu, Akihiko Yokohama, Takuma Ishizaki, Nahoko Hatsumi, Satoru Takada, Takayuki Saitoh, Toru Sakura, Yoshihisa Nojima, Hiroshi Handa
We retrospectively investigated 144 patients with relapsed acute myeloid leukemia (AML) to clarify predisposing factors and the prognostic impact of acquisition of additional cytogenetic abnormalities (ACA) at the first relapse. Additional cytogenetic abnormalities are recognized as clonal evolution at the cytogenetic level. Fifty-nine patients (41%) acquired ACA at the first relapse. The incidences of ACA acquisition varied depending on cytogenetic abnormalities at initial diagnosis. Multivariate analysis identified t(8;21), complex karyotype, and a duration of fewer than 12 months of complete remission as independent predisposing factors for ACA acquisition...
April 4, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28376920/molecular-clonality-analysis-of-esophageal-adenocarcinoma-by-multiregion-sequencing-of-tumor-samples
#17
Anna M J van Nistelrooij, Ronald van Marion, Linetta B Koppert, Katharina Biermann, Manon C W Spaander, Hugo W Tilanus, J Jan B van Lanschot, Bas P L Wijnhoven, Winand N M Dinjens
BACKGROUND: Intratumor heterogeneity has been demonstrated in several cancer types, following a model of branched evolution. It is unknown to which extent intratumor heterogeneity is applicable to esophageal adenocarcinoma. Therefore the aim of this study was to characterise intratumor heterogeneity in esophageal adenocarcinoma. METHODS: Multiregional targeted sequencing of four commonly altered genes was performed on 19 tumor regions collected from five esophageal adenocarcinomas...
April 4, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28375514/clinical-implications-of-genomic-adaptation-and-evolution-of-carbapenem-resistant-klebsiella-pneumoniae
#18
Angela Gomez-Simmonds, Anne-Catrin Uhlemann
Klebsiella pneumoniae poses a major challenge to healthcare worldwide as an important cause of multidrug-resistant infections. Nosocomial clones, including epidemic sequence type 258 (ST258), have shown an affinity for acquiring and disseminating resistance plasmids, particularly variants of the K. pneumoniae carbapenemase. By comparison, the resurgence of severe community-associated K. pneumoniae infections has led to increased recognition of hypervirulent strains belonging to the K1 and K2 capsular serotypes, predominantly in eastern Asia...
February 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28373404/precancer-atlas-to-drive-precision-prevention-trials
#19
Avrum Spira, Matthew B Yurgelun, Ludmil Alexandrov, Anjana Rao, Rafael Bejar, Kornelia Polyak, Marios Giannakis, Ali Shilatifard, Olivera J Finn, Madhav Dhodapkar, Neil E Kay, Esteban Braggio, Eduardo Vilar, Sarah A Mazzilli, Timothy R Rebbeck, Judy E Garber, Victor E Velculescu, Mary L Disis, Douglas C Wallace, Scott M Lippman
Cancer development is a complex process driven by inherited and acquired molecular and cellular alterations. Prevention is the holy grail of cancer elimination, but making this a reality will take a fundamental rethinking and deep understanding of premalignant biology. In this Perspective, we propose a national concerted effort to create a Precancer Atlas (PCA), integrating multi-omics and immunity - basic tenets of the neoplastic process. The biology of neoplasia caused by germline mutations has led to paradigm-changing precision prevention efforts, including: tumor testing for mismatch repair (MMR) deficiency in Lynch syndrome establishing a new paradigm, combinatorial chemoprevention efficacy in familial adenomatous polyposis (FAP), signal of benefit from imaging-based early detection research in high-germline risk for pancreatic neoplasia, elucidating early ontogeny in BRCA1-mutation carriers leading to an international breast cancer prevention trial, and insights into the intricate germline-somatic-immunity interaction landscape...
April 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28371598/natural-and-chemotherapy-induced-clonal-evolution-of-tumors
#20
REVIEW
M K Ibragimova, M M Tsyganov, N V Litviakov
Evolution and natural selection of tumoral clones in the process of transformation and the following carcinogenesis can be called natural clonal evolution. Its main driving factors are internal: genetic instability initiated by driver mutations and microenvironment, which enables selective pressure while forming the environment for cell transformation and their survival. We present our overview of contemporary research dealing with mechanisms of carcinogenesis in different localizations from precancerous pathologies to metastasis and relapse...
April 2017: Biochemistry. Biokhimii︠a︡
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