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Clonal evolution

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https://www.readbyqxmd.com/read/29776953/the-landscape-of-actionable-genomic-alterations-in-cell-free-circulating-tumor-dna-from-21-807-advanced-cancer-patients
#1
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/29772764/the-making-of-leukemia
#2
REVIEW
Inés González-Herrero, Guillermo Rodríguez-Hernández, Andrea Luengas-Martínez, Marta Isidro-Hernández, Rafael Jiménez, Maria Begoña García-Cenador, Francisco Javier García-Criado, Isidro Sánchez-García, Carolina Vicente-Dueñas
Due to the clonal nature of human leukemia evolution, all leukemic cells carry the same leukemia-initiating genetic lesions, independently of the intrinsic tumoral cellular heterogeneity. However, the latest findings have shown that the mode of action of oncogenes is not homogeneous throughout the developmental history of leukemia. Studies on different types of hematopoietic tumors have shown that the contribution of oncogenes to leukemia is mainly mediated through the epigenetic reprogramming of the leukemia-initiating target cell...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29771315/palimpsest-an-r-package-for-studying-mutational-and-structural-variant-signatures-along-clonal-evolution-in-cancer
#3
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/29766388/molecular-evolution-of-metaplasia-to-adenocarcinoma-in-the-esophagus
#4
REVIEW
William M Grady, Ming Yu
Esophageal adenocarcinoma (EAC) develops from Barrett's esophagus (BE), a condition where the normal squamous epithelia is replaced by specialized intestinal metaplasia in response to chronic gastroesophageal acid reflux. In a minority of individuals, BE can progress to low- and high-grade dysplasia and eventually to intra-mucosal and then invasive carcinoma. BE provides researchers with a unique model to characterize the process by which a carcinoma arises from its precursor lesion. Molecular studies of BE have demonstrated that it is not simply a metaplastic tissue, but rather it harbors frequent alterations that are also present in dysplastic BE and in EAC...
May 15, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29760902/exploring-the-evolution-of-multicellularity-in-saccharomyces-cerevisiae-under-bacteria-environment-an-experimental-phylogenetics-approach
#5
Julian F Quintero-Galvis, Rocío Paleo-López, Jaiber J Solano-Iguaran, María Josefina Poupin, Thomas Ledger, Juan Diego Gaitan-Espitia, Andrzej Antoł, Michael Travisano, Roberto F Nespolo
There have been over 25 independent unicellular to multicellular evolutionary transitions, which have been transformational in the complexity of life. All of these transitions likely occurred in communities numerically dominated by unicellular organisms, mostly bacteria. Hence, it is reasonable to expect that bacteria were involved in generating the ecological conditions that promoted the stability and proliferation of the first multicellular forms as protective units. In this study, we addressed this problem by analyzing the occurrence of multicellularity in an experimental phylogeny of yeasts ( Sacharomyces cerevisiae ) a model organism that is unicellular but can generate multicellular clusters under some conditions...
May 2018: Ecology and Evolution
https://www.readbyqxmd.com/read/29760052/spatial-mutation-patterns-as-markers-of-early-colorectal-tumor-cell-mobility
#6
Marc D Ryser, Byung-Hoon Min, Kimberly D Siegmund, Darryl Shibata
A growing body of evidence suggests that a subset of human cancers grows as single clonal expansions. In such a nearly neutral evolution scenario, it is possible to infer the early ancestral tree of a full-grown tumor. We hypothesized that early tree reconstruction can provide insights into the mobility phenotypes of tumor cells during their first few cell divisions. We explored this hypothesis by means of a computational multiscale model of tumor expansion incorporating the glandular structure of colorectal tumors...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29755956/preleukemia-and-leukemia-initiating-cell-activity-in-inv-16-acute-myeloid-leukemia
#7
REVIEW
John Anto Pulikkan, Lucio Hernán Castilla
Acute myeloid leukemia (AML) is a collection of hematologic malignancies with specific driver mutations that direct the pathology of the disease. The understanding of the origin and function of these mutations at early stages of transformation is critical to understand the etiology of the disease and for the design of effective therapies. The chromosome inversion inv(16) is thought to arise as a founding mutation in a hematopoietic stem cell (HSC) to produce preleukemic HSCs (preL-HSCs) with myeloid bias and differentiation block, and predisposed to AML...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29753882/circulating-tumor-microemboli-progress-in-molecular-understanding-and-enrichment-technologies
#8
REVIEW
Muhammad Umer, Ramanathan Vaidyanathan, Nam-Trung Nguyen, Muhammad J A Shiddiky
Circulating tumor cells (CTCs) and their clusters, also known as circulating tumor microemboli (CTM), have emerged as valuable tool that can provide mechanistic insights into the tumor heterogeneity, clonal evolution, and stochastic events within the metastatic cascade. However, recent investigations have hinted that CTM may not be mere aggregates of tumor cells but cells comprising CTM exhibit distinct phenotypic and molecular characteristics in comparison to single CTCs. Moreover, in many cases CTM demonstrated higher metastatic potential and resistance to apoptosis as compared to their single cell counterparts...
May 10, 2018: Biotechnology Advances
https://www.readbyqxmd.com/read/29751087/population-genetic-and-evolution-analysis-of-controversial-genus-edwardsiella-by-multilocus-sequence-typing
#9
Noemí Buján, Sabela Balboa, Jesús L Romalde, Alicia E Toranzo, Beatriz Magariños
At present, the genus Edwardsiella compiles five species: E. tarda, E. hoshinae, E. ictaluri, E. piscicida and E. anguillarum. Some species of this genus such us E. ictaluri and E. piscicida are important pathogens of numerous fish species. With the description of the two latter species, the phylogeny of Edwardsiella became more complicated. With the aim to clarify the relationships among all species in the genus, a multilocus sequence typing (MLST) approach was developed and applied to characterize 56 isolates and 6 reference strains belonging to the five Edwardsiella species...
May 8, 2018: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/29749763/clonal-evolution-of-philadelphia-chromosome-in-acute-myeloid-leukemia-after-azacitidine-treatment
#10
Meera Yogarajah, Nathan Montgomery, Melissa Matson, Laura Blanchard, Cassiopeia Frank, Sean Gallagher, Katherine Pepin, Lori Vaught, Benyam Muluneh, Matthew C Foster, Joshua F Zeidner
No abstract text is available yet for this article.
May 11, 2018: Leukemia & Lymphoma
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/29740480/estimating-the-intra-taxa-diversity-population-genetic-structure-and-evolutionary-pathways-of-cryptococcus-neoformans-and-cryptococcus-gattii
#12
Marina Muñoz, Milena Camargo, Juan D Ramírez
Members of the Cryptococcus complex, includes Cryptococcus neoformans (most common fungal infection of the brain) and Cryptococcus gattii (high-impact emerging pathogen worldwide). Currently, the fungal multilocus sequence typing database (Fungal MLST Database) constitutes a valuable data repository of the genes used for molecular typing of these pathogens. We analyzed the data available in the Fungal MLST Database for seven housekeeping genes, with the aim to evaluate its contribution in the description of intra-taxa diversity, population genetic structure, and evolutionary patterns...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29739401/limited-utility-of-tissue-micro-arrays-in-detecting-intra-tumoral-heterogeneity-in-stem-cell-characteristics-and-tumor-progression-markers-in-breast-cancer
#13
Pascale Kündig, Charlotte Giesen, Hartland Jackson, Bernd Bodenmiller, Bärbel Papassotirolopus, Sandra Nicole Freiberger, Catharine Aquino, Lennart Opitz, Zsuzsanna Varga
BACKGROUND: Intra-tumoral heterogeneity has been recently addressed in different types of cancer, including breast cancer. A concept describing the origin of intra-tumoral heterogeneity is the cancer stem-cell hypothesis, proposing the existence of cancer stem cells that can self-renew limitlessly and therefore lead to tumor progression. Clonal evolution in accumulated single cell genomic alterations is a further possible explanation in carcinogenesis. In this study, we addressed the question whether intra-tumoral heterogeneity can be reliably detected in tissue-micro-arrays in breast cancer by comparing expression levels of conventional predictive/prognostic tumor markers, tumor progression markers and stem cell markers between central and peripheral tumor areas...
May 8, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29736183/universality-of-clone-dynamics-during-tissue-development
#14
Steffen Rulands, Fabienne Lescroart, Samira Chabab, Christopher J Hindley, Nicole Prior, Magdalena K Sznurkowska, Meritxell Huch, Anna Philpott, Cedric Blanpain, Benjamin D Simons
The emergence of complex organs is driven by the coordinated proliferation, migration and differentiation of precursor cells. The fate behaviour of these cells is reflected in the time evolution their progeny, termed clones, which serve as a key experimental observable. In adult tissues, where cell dynamics is constrained by the condition of homeostasis, clonal tracing studies based on transgenic animal models have advanced our understanding of cell fate behaviour and its dysregulation in disease (1, 2). But what can be learned from clonal dynamics in development, where the spatial cohesiveness of clones is impaired by tissue deformations during tissue growth? Drawing on the results of clonal tracing studies, we show that, despite the complexity of organ development, clonal dynamics may converge to a critical state characterized by universal scaling behaviour of clone sizes...
May 2018: Nature Physics
https://www.readbyqxmd.com/read/29735988/evolution-of-invasiveness-by-genetic-accommodation
#15
Dan G Bock, Michael B Kantar, Celine Caseys, Remi Matthey-Doret, Loren H Rieseberg
Invasion success of species introduced to novel environments may be facilitated by adaptive evolution and by phenotypic plasticity. Here we investigate the independent and joint contribution of both mechanisms as drivers of invasiveness in the perennial sunflower Helianthus tuberosus. We show that invasive genotypes have multiple origins, and that invasive spread was facilitated by the repeated evolution of extreme values in a single trait, clonality. In line with genetic accommodation theory, we establish that this evolutionary transition occurred by refining a preexisting plastic response of clonality to water availability...
May 7, 2018: Nature Ecology & Evolution
https://www.readbyqxmd.com/read/29735827/molecular-characterisation-for-clonality-and-transmission-dynamics-of-an-outbreak-of-klebsiella-pneumoniae-amongst-neonates-in-a-tertiary-care-centre-in-south-india
#16
Chaitra Shankar, Manish Kumar, Ashtawarthani Baskaran, Miracle Magdelene Paul, Nithya Ponmudi, Sridhar Santhanam, Joy Sarojini Michael, Balaji Veeraraghavan
Purpose: Sepsis is a significant cause of morbidity and mortality amongst neonates. Klebsiella pneumoniae is a common cause of nosocomial outbreaks causing bacteraemia and having potential of acquiring plasmids enhancing antimicrobial resistance. In the present study, we investigate K. pneumoniae outbreak causing bacteraemia amongst neonates over a span of 2 months. Isolates were characterised for antimicrobial resistance, virulence, molecular typing for clonality and plasmid typing for transmission dynamics, and patient outcome was investigated...
January 2018: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29728368/-in-vivo-expansion-of-functionally-integrated-gabaergic-interneurons-by-targeted-increase-in-neural-progenitors
#17
Rachel E Shaw, Benjamin Kottler, Zoe N Ludlow, Edgar Buhl, Dongwook Kim, Sara Morais da Silva, Alina Miedzik, Antoine Coum, James Jl Hodge, Frank Hirth, Rita Sousa-Nunes
A central hypothesis for brain evolution is that it might occur via expansion of progenitor cells and subsequent lineage-dependent formation of neural circuits. Here, we report in vivo amplification and functional integration of lineage-specific circuitry in Drosophila Levels of the cell fate determinant Prospero were attenuated in specific brain lineages within a range that expanded not only progenitors but also neuronal progeny, without tumor formation. Resulting supernumerary neural stem cells underwent normal functional transitions, progressed through the temporal patterning cascade, and generated progeny with molecular signatures matching source lineages...
May 4, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29720713/treatment-resistance-in-urothelial-carcinoma-an-evolutionary-perspective
#18
REVIEW
Panagiotis J Vlachostergios, Bishoy M Faltas
The emergence of treatment-resistant clones is a critical barrier to cure in patients with urothelial carcinoma. Setting the stage for the evolution of resistance, urothelial carcinoma is characterized by extensive mutational heterogeneity, which is detectable even in patients with early stage disease. Chemotherapy and immunotherapy both act as selective pressures that shape the evolutionary trajectory of urothelial carcinoma throughout the course of the disease. A detailed understanding of the dynamics of evolutionary drivers is required for the rational development of curative therapies...
May 2, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29720585/de-novo-activating-mutations-drive-clonal-evolution-and-enhance-clonal-fitness-in-kmt2a-rearranged-leukemia
#19
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
https://www.readbyqxmd.com/read/29718735/expression-of-crbn-ikzf1-and-ikzf3-does-not-predict-lenalidomide-sensitivity-and-mutations-in-the-cereblon-pathway-are-infrequent-in-multiple-myeloma
#20
Konstantinos Dimopoulos, Helga Fibiger Munch-Petersen, Christian Winther Eskelund, Lene Dissing Sjö, Elisabeth Ralfkiaer, Peter Gimsing, Kirsten Grønbaek
The immunomodulatory drug thalidomide, and its analogs, lenalidomide, and pomalidomide (IMiDs), have become essential components of the standard treatment for multiple myeloma (MM), and have led to significant improvement of survival in patients with this devastating disease. Cereblon (CRBN), the direct target of IMiDs, has been proposed as a predictive biomarker of response to IMiDs. Using standard immunohistochemistry in formalin-fixed paraffin embedded (FFPE) bone marrow samples of 23 patients treated with a lenalidomide-containing regimen, we found that the malignant plasma cells of all the patients stained positive for CRBN, IKZF1, and IKZF3, regardless of sensitivity to IMiDs...
May 2, 2018: Leukemia & Lymphoma
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