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Clonal evolution

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https://www.readbyqxmd.com/read/29352488/understanding-intratumor-heterogeneity-by-combining-genome-analysis-and-mathematical-modeling
#1
REVIEW
Atsushi Niida, Satoshi Nagayama, Satoru Miyano, Koshi Mimori
Cancer is composed of multiple cell populations with different genomes. Each of the populations is called a clone (or subclone) and this phenomenon is called intratumor heterogeneity (ITH). ITH is observed in various types of cancers and presumed to be a major cause leading to therapeutic resistance. If a tumor harbors a major clone sensitive to a specific anti-cancer treatment, the tumor shrinks within a given period after the treatment. However, in most cases, a minor clone resistant to the chemotherapy exists in the tumor and predominantly regrows in spite of the intensive therapy...
January 20, 2018: Cancer Science
https://www.readbyqxmd.com/read/29351238/telomeres-implications-for-cancer-development
#2
REVIEW
Aina Bernal, Laura Tusell
Telomeres facilitate the protection of natural ends of chromosomes from constitutive exposure to the DNA damage response (DDR). This is most likely achieved by a lariat structure that hides the linear telomeric DNA through protein-protein and protein-DNA interactions. The telomere shortening associated with DNA replication in the absence of a compensatory mechanism culminates in unmasked telomeres. Then, the subsequent activation of the DDR will define the fate of cells according to the functionality of cell cycle checkpoints...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29346413/genetic-diversity-and-potential-routes-of-transmission-of-mycobacterium-bovis-in-mozambique
#3
Adelina Machado, Teresa Rito, Solomon Ghebremichael, Nuelma Muhate, Gabriel Maxhuza, Custodia Macuamule, Ivania Moiane, Baltazar Macucule, Angelica Suzana Marranangumbe, Jorge Baptista, Joaquim Manguele, Tuija Koivula, Elizabeth Maria Streicher, Robin Mark Warren, Gunilla Kallenius, Paul van Helden, Margarida Correia-Neves
Bovine tuberculosis is a zoonotic disease with largely unknown impact in Africa, with risk factors such as HIV and direct contact with animals or consumption of Mycobacterium bovis infected animal products. In order to understand and quantify this risk and design intervention strategies, good epidemiological studies are needed. Such studies can include molecular typing of M. bovis isolates. The aim of this study was to apply these tools to provide novel information concerning the distribution of bovine tuberculosis in cattle in Mozambique and thereby provide relevant information to guide policy development and strategies to contain the disease in livestock, and reduce the risk associated with transmission to humans...
January 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29345308/positive-size-speed-relationships-in-gametes-and-vegetative-cells-of-chlamydomonas-reinhardtii-implications-for-the-evolution-of-sperm
#4
Catherine E Seed, Joseph L Tomkins
It is commonly held that differences in gametes of the two sexes (anisogamy) evolved from ancestors whose gametes were similar in size and behaviour (isogamy). Underlying many hypotheses explaining anisogamy are assumed relationships between cell size and speed in the ancestral isogamous population. Using the isogamous alga Chlamydomonas reinhardtii, we explored size-speed distributions in vegetative and gamete cells of ten cell lines, and clonal data from within two cell lines. We applied an independent speed selection approach to gamete populations of C...
January 18, 2018: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/29345018/an-orphan-protist-quadricilia-rotundata-finally-finds-its-phylogenetic-home-in-cercozoa
#5
Akinori Yabuki, Ken-Ichiro Ishida
Quadricilia rotundata is a heterotrophic flagellate with four flagella. However, because this species has no clear morphological characteristics or molecular data affiliating it with any known group, Q. rotundata has been treated as a protist incertae sedis, for a long time. Here, we established a clonal culture of Q. rotundata and sequenced its 18S rDNA sequence. Molecular phylogenetic analysis successfully placed Q. rotundata in an environmental clade within Cercozoa, which contributes to expand the morphological and species diversity within Cercozoa...
January 18, 2018: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/29344954/mixed-ductal-lobular-carcinomas-evidence-for-progression-from-ductal-to-lobular-morphology
#6
Amy E McCart Reed, Jamie R Kutasovic, Katia Nones, Jodi M Saunus, Leonard Da Silva, Felicity Newell, Stephen Kazakoff, Lewis Melville, Janani Jayanthan, Ana Cristina Vargas, Lynne E Reid, Jonathan Beesley, Xiao Qing Chen, Anne Marie Patch, D David Clouston, Alan Porter, Elizabeth Evans, John V Pearson, Georgia Chenevix-Trench, Margaret C Cummings, Nic Waddell, Sunil R Lakhani, Peter T Simpson
Mixed ductal-lobular carcinomas (MDL) display both ductal and lobular morphology, and are an archetypal example of intra-tumour morphological heterogeneity. The mechanisms underlying coexistence of these different morphologic entities are poorly understood, although theories include that these components either represent 'collision' of independent tumours or evolve from a common ancestor. We performed comprehensive clinico-pathological analysis of a cohort of 82 MDLs and found: i) MDLs more frequently co-exist with ductal carcinoma in situ (DCIS) than lobular carcinoma in situ (LCIS); ii) the E-cadherin-catenin complex was normal in the ductal component in 77...
January 18, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29342233/quantumclone-clonal-assessment-of-functional-mutations-in-cancer-based-on-a-genotype-aware-method-for-clonal-reconstruction
#7
Paul Deveau, Leo Colmet Daage, Derek Oldridge, Virginie Bernard, Angela Bellini, Mathieu Chicard, Nathalie Clement, Eve Lapouble, Valerie Combaret, Anne Boland, Vincent Meyer, Jean-Francois Deleuze, Isabelle Janoueix-Lerosey, Emmanuel Barillot, Olivier Delattre, John Maris, Gudrun Schleiermacher, Valentina Boeva
Motivation: In cancer, clonal evolution is assessed based on information coming from single nucleotide variants and copy number alterations. Nonetheless, existing methods often fail to accurately combine information from both sources to truthfully reconstruct clonal populations in a given tumor sample or in a set of tumor samples coming from the same patient. Moreover, previously published methods detect clones from a single set of variants. As a result, compromises have to be done between stringent variant filtering (reducing dispersion in variant allele frequency estimates, VAFs) and using all biologically relevant variants...
January 12, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29342136/clonal-evolution-mechanisms-in-nt5c2-mutant-relapsed-acute-lymphoblastic-leukaemia
#8
Gannie Tzoneva, Chelsea L Dieck, Koichi Oshima, Alberto Ambesi-Impiombato, Marta Sánchez-Martín, Chioma J Madubata, Hossein Khiabanian, Jiangyan Yu, Esme Waanders, Ilaria Iacobucci, Maria Luisa Sulis, Motohiro Kato, Katsuyoshi Koh, Maddalena Paganin, Giuseppe Basso, Julie M Gastier-Foster, Mignon L Loh, Renate Kirschner-Schwabe, Charles G Mullighan, Raul Rabadan, Adolfo A Ferrando
Relapsed acute lymphoblastic leukaemia (ALL) is associated with resistance to chemotherapy and poor prognosis. Gain-of-function mutations in the 5'-nucleotidase, cytosolic II (NT5C2) gene induce resistance to 6-mercaptopurine and are selectively present in relapsed ALL. Yet, the mechanisms involved in NT5C2 mutation-driven clonal evolution during the initiation of leukaemia, disease progression and relapse remain unknown. Here we use a conditional-and-inducible leukaemia model to demonstrate that expression of NT5C2(R367Q), a highly prevalent relapsed-ALL NT5C2 mutation, induces resistance to chemotherapy with 6-mercaptopurine at the cost of impaired leukaemia cell growth and leukaemia-initiating cell activity...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29340211/differences-in-adaptive-dynamics-determine-the-success-of-virus-variants-that-propagate-together
#9
María Arribas, Jacobo Aguirre, Susanna Manrubia, Ester Lázaro
Virus fitness is a complex parameter that results from the interaction of virus-specific characters (e.g. intracellular growth rate, adsorption rate, virion extracellular stability, and tolerance to mutations) with others that depend on the underlying fitness landscape and the internal structure of the whole population. Individual mutants usually have lower fitness values than the complex population from which they come from. When they are propagated and allowed to attain large population sizes for a sufficiently long time, they approach mutation-selection equilibrium with the concomitant fitness gains...
January 2018: Virus Evolution
https://www.readbyqxmd.com/read/29334678/genome-evolution-analysis-of-recurrent-testicular-malignant-mesothelioma-by-whole-genome-sequencing
#10
Shigeng Zhang, Qi Zhang, Qing Sun, Jinlong Tang, Jimin Chen, Na Ji, Yichun Zheng, Francia Fang, Wanjun Lei, Pengpeng Li, Nan Zhang
BACKGROUND/AIMS: Malignant mesothelioma of the tunica vaginalis testis is a rare and lethal disease. The genomic characteristics and genetic changes of tumor cells during the progression of this disease are unknown. METHODS: we performed whole-genome sequencing of four successive tumor samples derived from surgery and a blood sample in a single patient. RESULTS: All tumors were found to have significant C-to-T and T-to-C mutations, and amplification of copy number in chromosomes 1 and 12 were notified in all tumor samples...
January 15, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29332326/carcinogenic-potential-of-antitumor-therapies-is-the-risk-predictable
#11
Ivanka Nenova, Janet Grudeva-Popova
The growing number of successfully cured cancer patients has created a new field in oncogenesis. The life expectancy of such patients has increased, however this favorable event may create enough time for epigenetic events to occur which can cause a new carcinognic event, i.e. a secondary malignancy. The terms in use are second primary malignancies as well as therapy-related neoplasms in case the treatment of the first neoplasm is a direct cause. Second primary malignancies can be hematological neoplasms or solid tumors, with solid tumors having higher frequency...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331019/cis-regulator-runaway-and-divergence-in-asexuals
#12
Frédéric Fyon, Thomas Lenormand
With the advent of new sequencing technologies, the evolution of gene expression is becoming a subject of intensive genomic research, with sparking debates upon the role played by these kinds of changes in adaptive evolution and speciation. In this paper, we model expression evolution in species differing by their reproductive systems. We consider different rates of sexual versus asexual reproduction and the different type of parthenogenesis (apomixis and the various modes of automixis). We show that competition for expression leads to two selective processes on cis-regulatory regions that act independently to organism-level adaptation...
January 13, 2018: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/29328787/immune-responses-to-retroviruses
#13
Asier Saez-Cirion, Nicolas Manel
Retroviruses are genome invaders that have shared a long history of coevolution with vertebrates and their immune system. Found endogenously in genomes as traces of past invasions, retroviruses are also considerable threats to human health when they exist as exogenous viruses such as HIV. The immune response to retroviruses is engaged by germline-encoded sensors of innate immunity that recognize viral components and damage induced by the infection. This response develops with the induction of antiviral effectors and launching of the clonal adaptive immune response, which can contribute to protective immunity...
January 12, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29327728/diverse-modes-of-clonal-evolution-in-hbv-related-hepatocellular-carcinoma-revealed-by-single-cell-genome-sequencing
#14
Meng Duan, Junfeng Hao, Sijia Cui, Daniel L Worthley, Shu Zhang, Zhichao Wang, Jieyi Shi, Longzi Liu, Xiaoying Wang, Aiwu Ke, Ya Cao, Ruibin Xi, Xiaoming Zhang, Jian Zhou, Jia Fan, Chong Li, Qiang Gao
Hepatocellular carcinoma (HCC) is a cancer of substantial morphologic, genetic and phenotypic diversity. Yet we do not understand the relationship between intratumor heterogeneity and the associated morphologic/histological characteristics of the tumor. Using single-cell whole-genome sequencing to profile 96 tumor cells (30-36 each) and 15 normal liver cells (5 each), collected from three male patients with HBV-associated HCC, we confirmed that copy number variations occur early in hepatocarcinogenesis but thereafter remain relatively stable throughout tumor progression...
January 12, 2018: Cell Research
https://www.readbyqxmd.com/read/29324785/phylogenetic-diversity-antimicrobial-susceptibility-and-virulence-gene-profiles-of-brachyspira-hyodysenteriae-isolates-from-pigs-in-germany
#15
Jessica Joerling, Stefanie A Barth, Karen Schlez, Hermann Willems, Werner Herbst, Christa Ewers
Swine dysentery (SD) is an economically important diarrheal disease in pigs caused by different strongly hemolytic Brachyspira (B.) species, such as B. hyodysenteriae, B. suanatina and B. hampsonii. Possible associations of epidemiologic data, such as multilocus sequence types (STs) to virulence gene profiles and antimicrobial susceptibility are rather scarce, particularly for B. hyodysenteriae isolates from Germany. In this study, B. hyodysenteriae (n = 116) isolated from diarrheic pigs between 1990 and 2016 in Germany were investigated for their STs, susceptibility to the major drugs used for treatment of SD (tiamulin and valnemulin) and genes that were previously linked with virulence and encode for hemolysins (tlyA, tlyB, tlyC, hlyA, BHWA1_RS02885, BHWA1_RS09085, BHWA1_RS04705, and BHWA1_RS02195), outer membrane proteins (OMPs) (bhlp16, bhlp17...
2018: PloS One
https://www.readbyqxmd.com/read/29321904/offspring-of-older-parents-are-smaller-but-no-less-bilaterally-symmetrical-than-offspring-of-younger-parents-in-the-aquatic-plant-lemna-turionifera
#16
Eric J Ankutowicz, Robert A Laird
Offspring quality decreases with parental age in many taxa, with offspring of older parents exhibiting reduced life span, reproductive capacity, and fitness, compared to offspring of younger parents. These "parental age effects," whose consequences arise in the next generation, can be considered as manifestations of parental senescence, in addition to the more familiar age-related declines in parent-generation survival and reproduction. Parental age effects are important because they may have feedback effects on the evolution of demographic trajectories and longevity...
January 2018: Ecology and Evolution
https://www.readbyqxmd.com/read/29317634/punctuated-evolution-of-canonical-genomic-aberrations-in-uveal-melanoma
#17
Matthew G Field, Michael A Durante, Hima Anbunathan, Louis Z Cai, Christina L Decatur, Anne M Bowcock, Stefan Kurtenbach, J William Harbour
Cancer is thought to arise through the accumulation of genomic aberrations evolving under Darwinian selection. However, it remains unclear when the aberrations associated with metastasis emerge during tumor evolution. Uveal melanoma (UM) is the most common primary eye cancer and frequently leads to metastatic death, which is strongly linked to BAP1 mutations. Accordingly, UM is ideally suited for studying the clonal evolution of metastatic competence. Here we analyze sequencing data from 151 primary UM samples using a customized bioinformatic pipeline, to improve detection of BAP1 mutations and infer the clonal relationships among genomic aberrations...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29316828/hodgkin-s-lymphoma-and-its-association-with-ebv-and-hiv-infection
#18
Ravnit Grewal, Alexandra Irimie, Nasheen Naidoo, Nooroudien Mohamed, Bobe Petrushev, Manogari Chetty, Ciprian Tomuleasa, Emmanuel-Akinola Abayomi
Hodgkin's lymphoma (HL) constitutes a clonal expansion of what appears to be malignant B cells. Viruses are involved in its pathogenesis, such as the Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV). Since these viral infections have been shown to play key roles in the pathogenesis of HL, countries with a prevalence of HIV and EBV represent interesting population targets to study the pathogenesis of HL, linking the evolution of the disease with viral infections. Usually, patients present with late stage disease often involving the bone marrow at the time of diagnosis...
January 9, 2018: Critical Reviews in Clinical Laboratory Sciences
https://www.readbyqxmd.com/read/29312603/intratumoral-heterogeneity-and-tert-promoter-mutations-in-progressive-higher-grade-meningiomas
#19
Tareq A Juratli, Christian Thiede, Mara V A Koerner, Shilpa S Tummala, Dirk Daubner, Ganesh M Shankar, Erik A Williams, Maria Martinez-Lage, Silke Soucek, Katja Robel, Tristan Penson, Mechthild Krause, Steffen Appold, Matthias Meinhardt, Thomas Pinzer, Julie J Miller, Dietmar Krex, Heather A Ely, Ian M Silverman, Jason Christiansen, Gabriele Schackert, Hiroaki Wakimoto, Matthias Kirsch, Priscilla K Brastianos, Daniel P Cahill
Background: Recent studies have reported mutations in the telomerase reverse transcriptase promoter (TERTp) in meningiomas. We sought to determine the frequency, clonality and clinical significance of telomere gene alterations in a cohort of patients with progressive/higher-grade meningiomas. Methods: We characterized 64 temporally- and regionally-distinct specimens from 26 WHO grade III meningioma patients. On initial diagnoses, the meningiomas spanned all WHO grades (3 grade I, 13 grade II and 10 grade III)...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311096/early-detection-and-evolution-of-pre-leukemic-clones-in-therapy-related-myeloid-neoplasms-following-autologous-sct
#20
Gerbrig Berger, Leonie I Kroeze, Theresia N Koorenhof-Scheele, Aniek O de Graaf, Kenichi Yoshida, Hiroo Ueno, Yuichi Shiraishi, Satoru Miyano, Eva van den Berg, Hein Schepers, Bert A van der Reijden, Seishi Ogawa, Edo Vellenga, Joop H Jansen
Therapy-related myeloid neoplasms (tMNs) are severe adverse events that can occur following treatment with autologous hematopoietic stem cell transplantation (ASCT). This study aimed to investigate the development of tMN following ASCT at the molecular level by whole exome sequencing (WES) and targeted deep sequencing (TDS) in sequential (pre-) tMN samples. WES identified a significantly higher number of mutations in tMN as compared to de novo MDS (median 27 vs 12, p=0.001). The mutations found in tMN did not carry a clear ageing-signature, unlike the mutations found in de novo MDS, indicating a different mutational mechanism...
January 8, 2018: Blood
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