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https://www.readbyqxmd.com/read/27923066/somatic-genomics-and-clinical-features-of-lung-adenocarcinoma-a-retrospective-study
#1
Jianxin Shi, Xing Hua, Bin Zhu, Sarangan Ravichandran, Mingyi Wang, Cu Nguyen, Seth A Brodie, Alessandro Palleschi, Marco Alloisio, Gianluca Pariscenti, Kristine Jones, Weiyin Zhou, Aaron J Bouk, Joseph Boland, Belynda Hicks, Adam Risch, Hunter Bennett, Brian T Luke, Lei Song, Jubao Duan, Pengyuan Liu, Takashi Kohno, Qingrong Chen, Daoud Meerzaman, Crystal Marconett, Ite Laird-Offringa, Ian Mills, Neil E Caporaso, Mitchell H Gail, Angela C Pesatori, Dario Consonni, Pier Alberto Bertazzi, Stephen J Chanock, Maria Teresa Landi
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression. METHODS AND FINDINGS: We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923045/tumor-evolution-in-two-patients-with-basal-like-breast-cancer-a-retrospective-genomics-study-of-multiple-metastases
#2
Katherine A Hoadley, Marni B Siegel, Krishna L Kanchi, Christopher A Miller, Li Ding, Wei Zhao, Xiaping He, Joel S Parker, Michael C Wendl, Robert S Fulton, Ryan T Demeter, Richard K Wilson, Lisa A Carey, Charles M Perou, Elaine R Mardis
BACKGROUND: Metastasis is the main cause of cancer patient deaths and remains a poorly characterized process. It is still unclear when in tumor progression the ability to metastasize arises and whether this ability is inherent to the primary tumor or is acquired well after primary tumor formation. Next-generation sequencing and analytical methods to define clonal heterogeneity provide a means for identifying genetic events and the temporal relationships between these events in the primary and metastatic tumors within an individual...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923043/clonal-evolutionary-analysis-during-her2-blockade-in-her2-positive-inflammatory-breast-cancer-a-phase-ii-open-label-clinical-trial-of-afatinib-vinorelbine
#3
Gerald Goh, Ramona Schmid, Kelly Guiver, Wichit Arpornwirat, Imjai Chitapanarux, Vinod Ganju, Seock-Ah Im, Sung-Bae Kim, Arunee Dechaphunkul, Jedzada Maneechavakajorn, Neil Spector, Thomas Yau, Mehdi Afrit, Slim Ben Ahmed, Stephen R Johnston, Neil Gibson, Martina Uttenreuther-Fischer, Javier Herrero, Charles Swanton
BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27913475/molecular-monitoring-in-chronic-myeloid-leukemia-how-low-can-you-go
#4
Susan Branford
Molecular monitoring of BCR-ABL1 transcripts for patients with chronic myeloid leukemia (CML) is now used to assess response to tyrosine kinase inhibitors (TKIs), including treatment failure that mandates a change of therapy. Therefore, many centers have adopted the molecular technique for measuring BCR-ABL1 and rely on conversion of values to the international reporting scale for appropriate clinical interpretation. However, the technique has a degree of inherent variability despite standardized procedures, which means care should be taken by the clinician when assessing response based on BCR-ABL1 cutoff limits...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913467/transplantation-for-bone-marrow-failure-current-issues
#5
Régis Peffault de Latour
The preferred treatment of idiopathic aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA)-identical sibling donor. Transplantation from a well-matched unrelated donor (MUD) may be considered for patients without a sibling donor after failure of immunosuppressive therapy, as may alternative transplantation (mismatched, cord blood or haplo-identical HSCT) for patients without a MUD. HSCT may also be contemplated for congenital disorders in cases of pancytopenia or severe isolated cytopenia...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913466/nontransplant-therapy-for-bone-marrow-failure
#6
Danielle M Townsley, Thomas Winkler
Nontransplant therapeutic options for acquired and constitutional aplastic anemia have significantly expanded during the last 5 years. In the future, transplant may be required less frequently. That trilineage hematologic responses could be achieved with the single agent eltrombopag in refractory aplastic anemia promotes new interest in growth factors after years of failed trials using other growth factor agents. Preliminary results adding eltrombopag to immunosuppressive therapy are promising, but long-term follow-up data evaluating clonal evolution rates are required before promoting its standard use in treatment-naive disease...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913465/aplastic-anemia-and-clonal-evolution-germ-line-and-somatic-genetics
#7
Akiko Shimamura
Clonal progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) remains a dreaded complication for a subset of patients with bone marrow failure (BMF). Recognizing risk factors for the development of MDS or AML would inform individualized treatment decisions and identify patients who may benefit from early or upfront hematopoietic stem cell transplantation. Now that next-generation DNA sequencing is available in the clinical laboratory, research has focused on the implications of germ line and somatic mutations for diagnosing and monitoring patients with BMF...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913420/multiple-evolutionary-trajectories-have-led-to-the-emergence-of-races-in-fusarium-oxysporum-f-sp-lycopersici
#8
Biju V Chellappan, Like Fokkens, Petra M Houterman, Martijn Rep, Ben J C Cornelissen
: Race 1 isolates of Fusarium oxysporum f. sp. lycopersici (Fol) are characterized by the presence of AVR1 in their genome. The product of this gene, Avr1, triggers resistance in tomato cultivars carrying resistance gene I In Fol race 2 and race 3 isolates, AVR1 is absent and hence they are virulent on tomato cultivars carrying I In this study, we analyze an approximately 100 kb genomic fragment containing the AVR1 locus of race 1 isolate Fol004, and compare it to the sequenced genome of Fol race 2 isolate 4287 (Fol4287)...
December 2, 2016: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/27911792/transcriptomics-and-neuroanatomy-of-the-clonal-raider-ant-implicate-an-expanded-clade-of-odorant-receptors-in-chemical-communication
#9
Sean K McKenzie, Ingrid Fetter-Pruneda, Vanessa Ruta, Daniel J C Kronauer
A major aim of sociogenomic research is to uncover common principles in the molecular evolution of sociality. This endeavor has been hampered by the small number of specific genes currently known to function in social behavior. Here we provide several lines of evidence suggesting that ants have evolved a large and novel clade of odorant receptor (OR) genes to perceive hydrocarbon-based pheromones, arguably the most important signals in ant communication. This genomic expansion is also mirrored in the ant brain via a corresponding expansion of a specific cluster of glomeruli in the antennal lobe...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911124/the-impact-of-interferon-alpha2-on-hla-genes-in-patients-with-polycythemia-vera-and-related-neoplasms
#10
Vibe Skov, Caroline Hasselbalch Riley, Mads Thomassen, Lasse Kjær, Thomas Stauffer Larsen, Ole Weis Bjerrum, Torben A Kruse, Hans Carl Hasselbalch
Gene expression profiling in Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have unraveled significant deregulation of several immune and inflammation genes of potential importance for clonal evolution. Other mechanisms might be downregulation of major histocompatibility class I and II genes used by tumor cells to escape antitumor T-cell-mediated immune responses. Several genes encoding human leukocyte antigen (HLA) class I and II molecules have been shown to be significantly downregulated...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27910010/chromosome-preparation-for-myeloid-malignancies
#11
Eleanor K C Hui, Thomas S K Wan, Margaret H L Ng
Many cases of myeloid malignancies are associated with recurring cytogenetic aberrations. Chromosomal analysis can aid in diagnosis, predict prognosis, and disclose subsequent clonal evolution. Three different cell culture methods: direct harvest, nonsynchronized culture, and synchronized culture are usually prepared if the nucleated cell counts in marrow blood are sufficient. Synchronized culture is the first choice of method in myeloid malignancies, whereas the direct method can be omitted if the cell count is low...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27910009/cancer-cytogenetics-an-introduction
#12
Thomas S K Wan
The Philadelphia chromosome was the first chromosomal abnormality discovered in cancer using the cytogenetics technique in 1960, and was consistently associated with chronic myeloid leukemia. Over the past five decades, innovative technical advances in the field of cancer cytogenetics have greatly enhanced the detection ability of chromosomal alterations, and have facilitated the research and diagnostic potential of chromosomal studies in neoplasms. These developments notwithstanding, chromosome analysis of a single cell is still the easiest way to delineate and understand the relationship between clonal evolution and disease progression of cancer cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909934/current-achievements-and-future-perspectives-of-metronomic-chemotherapy
#13
REVIEW
Adriana Romiti, Rosa Falcone, Michela Roberto, Paolo Marchetti
In recent years, many anticancer drugs have been tested at metronomic dosages for a variety of tumours. Mechanisms of action attributed to metronomic chemotherapy (MCT) include antiangiogenesis, immunomodulation, direct inhibition of tumour growth, effect on tumour initiating cells and the modulation of clonal evolution. An active clinical research, aimed at testing MCT in several cancers, has been conducted over the past 15 years. However, because the majority of available results come from earlier phase II studies, mainly performed in the area of breast cancer (BC), it is clear that there are areas still to be investigated...
December 1, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27908747/tci-tcii-and-tcvi-trypanosoma-cruzi-samples-from-chagas-disease-patients-with-distinct-clinical-forms-and-critical-analysis-of-in-vitro-and-in-vivo-behavior-response-to-treatment-and-infection-evolution-in-murine-model
#14
Maykon Tavares de Oliveira, Renata Tupinambá Branquinho, Gláucia Diniz Aléssio, Carlos Geraldo Campos Mello, Nívia Carolina Nogueira de Paiva, Cláudia Martins Carneiro, Max Jean de Ornelas Toledo, Alexandre Barbosa Reis, Olindo Assis Martins Filho, Marta de Lana
The clonal evolution of Trypanosoma cruzi sustains scientifically the hypothesis of association between parasite's genetic, biological behavior and possibly the clinical aspects of Chagas disease in patients from whom they were isolated. This study intended to characterize a range of biological properties of TcI, TcII and TcVI T. cruzi samples in order to verify the existence of these associations. Several biological features were evaluated, including in vitro epimastigote-growth, "Vero"cells infectivity and growth, along with in vivo studies of parasitemia, polymorphism of trypomastigotes, cardiac inflammation, fibrosis and response to treatment by nifurtimox during the acute and chronic murine infection...
November 28, 2016: Acta Tropica
https://www.readbyqxmd.com/read/27904879/the-establishment-and-diversification-of-epidemic-associated-serogroup-w-meningococcus-in-the-african-meningitis-belt-1994-to-2012
#15
Adam C Retchless, Fang Hu, Abdoul-Salam Ouédraogo, Seydou Diarra, Kristen Knipe, Mili Sheth, Lori A Rowe, Lassana Sangaré, Absetou Ky Ba, Soumeya Ouangraoua, Dhwani Batra, Ryan T Novak, Rasmata Ouédraogo Traoré, Xin Wang
Epidemics of invasive meningococcal disease (IMD) caused by meningococcal serogroup A have been eliminated from the sub-Saharan African so-called "meningitis belt" by the meningococcal A conjugate vaccine (MACV), and yet, other serogroups continue to cause epidemics. Neisseria meningitidis serogroup W remains a major cause of disease in the region, with most isolates belonging to clonal complex 11 (CC11). Here, the genetic variation within and between epidemic-associated strains was assessed by sequencing the genomes of 92 N...
November 2016: MSphere
https://www.readbyqxmd.com/read/27904775/disease-evolution-and-heterogeneity-in-bilateral-breast-cancer
#16
Elena Fountzilas, Vassiliki Kotoula, Flora Zagouri, Eleni Giannoulatou, George Kouvatseas, George Pentheroudakis, Triantafyllia Koletsa, Mattheos Bobos, Kyriaki Papadopoulou, Epaminontas Samantas, Efterpi Demiri, Spyros Miliaras, Christos Christodoulou, Sofia Chrisafi, Evangelia Razis, Florentia Fostira, Dimitrios Pectasides, George Zografos, George Fountzilas
Bilateral breast cancers (BBC) are currently treated as independent tumors arising in the same patient. Herein, we investigated whether BBC indeed evolve independently at the genomic level. We examined paired targeted next generation sequencing genotypes from 155 paraffin tumors corresponding to 76 BBC patients (75 women and one man; 52 concurrent and 24 metachronous), for coding mutations (amino acid changing, minor allele frequency <0.1%) and single nucleotide polymorphism (SNP) zygosity. Germline genotypes were available for 29 patients...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27899806/preleukemia-one-name-many-meanings
#17
REVIEW
H P Koeffler, G Leong
Definition of preleukemia has evolved. It was first used to describe the myelodysplastic syndrome (MDS) with a propensity to progress to acute myeloid leukemia (AML). Individuals with germline mutations of either RUNX1, CEBPA, or GATA2 can also be called as preleukemic because they have a markedly increased incidence of evolution into AML. Also, alkylating chemotherapy or radiation can cause MDS/preleukemia which nearly always progress to AML. More recently investigators noted that AML patients who achieved complete morphological remission after chemotherapy often have clonal hematopoiesis predominantly marked by either DNMT3A, TET2 or IDH1/2 mutations which were also present at diagnosis of AML...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27895712/philadelphia-chromosome-duplication-as-a-ring-shaped-chromosome
#18
Cesar Borjas-Gutierrez, Juan Ramon Gonzalez-Garcia
The gain of a second copy of the Philadelphia chromosome is one of the main secondary chromosomal changes related to the clonal evolution of cells with t(9;22) in chronic myelogenous leukemia. This gain causes the acquisition of another copy of the BCR/ABL1 fusion gene. Isochromosomes of the der(22) chromosome or double minute chromosomes are well known to lead an increased copy number of BCR/ABL1 gene. There is no antecedent of Philadelphia chromosome duplication as a ring chromosome. A recent published report contains evidence that strongly suggests that the Philadelphia chromosome was duplicated as a ring chromosome, observation that was overlooked by the authors...
2016: Molecular Cytogenetics
https://www.readbyqxmd.com/read/27888620/identification-of-different-alk-mutations-in-a-pair-of-neuroblastoma-cell-lines-established-at-diagnosis-and-relapse
#19
Lindi Chen, Angharad Humphreys, Lisa Turnbull, Angela Bellini, Gudrun Schleiermacher, Helen Salwen, Susan L Cohn, Nick Bown, Deborah A Tweddle
Anaplastic Lymphoma Kinase (ALK) is a transmembrane receptor kinase that belongs to the insulin receptor superfamily and has previously been shown to play a role in cell proliferation, migration and invasion in neuroblastoma. Activating ALK mutations are reported in both hereditary and sporadic neuroblastoma tumours, and several ALK inhibitors are currently under clinical evaluation as novel treatments for neuroblastoma. Overall, mutations at codons F1174, R1275 and F1245 together account for ~85% of reported ALK mutations in neuroblastoma...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888226/single-cell-sequencing-maps-gene-expression-to-mutational-phylogenies-in-pdgf-and-egf-driven-gliomas
#20
Sören Müller, Siyuan John Liu, Elizabeth Di Lullo, Martina Malatesta, Alex A Pollen, Tomasz J Nowakowski, Gary Kohanbash, Manish Aghi, Arnold R Kriegstein, Daniel A Lim, Aaron Diaz
Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor. Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) receptors are frequently amplified and/or possess gain-of-function mutations in GBM However, clinical trials of tyrosine-kinase inhibitors have shown disappointing efficacy, in part due to intra-tumor heterogeneity. To assess the effect of clonal heterogeneity on gene expression, we derived an approach to map single-cell expression profiles to sequentially acquired mutations identified from exome sequencing...
November 25, 2016: Molecular Systems Biology
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