DOCSLIB.ORG

Abstracts Book

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Abstracts Book Meeting July 29-August 3, 2014 – University of Washington, Seattle Abstracts Book Conference Organizers Trisha Davis, Chair Mike Snyder, Co-chair Program Committee Karen Arndt Leonid Kruglyak Dave Toczyski Sue Biggins Michael Lichten Phong Tran Orna Cohen-Fix Vicki Lundblad Olga Troyanskaya Liz Conibear Mike McMurray Toshi Tsukiyama Maitreya Dunham Yoshi Ohya Fred van Leeuwen Richard Gardner Steve Oliver Eric Weiss Tim Hughes Peter Stirling Mobile website: http://y.gsaconf.org Follow the conference on Twitter: #YEAST14 Genetics Society of America 9650 Rockville Pike, Bethesda, Maryland 20814-3998 Telephone: (301) 634-7300 • Toll-free: (866) 486-4363 • Fax: (301) 634-7079 E-mail: [email protected] • Website: genetics-gsa.org 1. The structure of an Ndr/LATS kinase - Mob complex reveals a novel kinase-coactivator system and substrate docking mechanism. Kyle Schneider1, Gergõ Gógl2, Brian Yeh1, Nashida Alam1, Alex Nguyen Ba3, Alan Moses3, Csaba Hetenyi2, Attila Reményi2, Eric Weiss1. 1) Molecular Biosciences, Northwestern University, Evanston, IL; 2) Institute of Enzymology, Hungarian Academy of Sciences, Budapest; 3) Department of Cell & Systems Biology, University of Toronto. Hippo signaling pathways are ancient in eukaryotes; they perform crucial functions in the control of cell proliferation and morphogenesis. In budding yeast, a form of hippo signaling called the RAM network controls the final event of mother/daughter separation and modulates polarized growth. In all hippo pathways, NDR/LATS kinases in complex with Mob coactivator proteins are key regulators of downstream target proteins. To understand how these enzymes are regulated and recognize in vivo substrates we solved the structure of the budding yeast Cbk1-Mob2 complex in three different crystal forms, providing the first structural template of an NDR/LATS kinase - Mob coactivator assembly. These structures suggest that Mob coactivator association allows NDR/LATS enzymes to use a novel adaptation of an AGC kinase activation mechanism that involves a highly conserved hydrophobic C-terminal motif. We have also discovered that the kinase domain of Cbk1 engages in a docking interaction with a short peptide motif present in its two known substrates, Ssd1 and Ace2, and have defined the surface of the kinase involved in this interaction. We find that the conserved docking motifs in Ace2 and Ssd1 enhance robustness of their control by Cbk1. Furthermore, examination of docking motif co-evolution with phosphorylation consensus motifs indicates that docking motif conservation strongly indicates that a protein is an in vivo Cbk1 regulatory target. This highlights an expanded set of seven high-confidence RAM network regulatory targets that form a functionally related group of effectors present at the site of cytokinesis. Analysis of a number of substrate orthologs across a wide range of fungi supports a sequential model for adaptive evolution of kinase docking, in which substrates first gain phosphorylation consensus sites and subsequently acquire docking motifs in otherwise rapidly changing unstructured regions. 2. Morphogenesis checkpoint kinase Swe1 is the executor of lipolysis-dependent cell cycle progression. Sepp D. Kohlwein, Neha Chauhan, Myriam Visram. Institute of Molecular Biosciences, University of Graz, Graz, Austria. Cell growth and division requires the precise duplication of cellular DNA content, but also of membranes and organelles. Knowledge about the cell cycle-dependent regulation of membrane and storage lipid homeostasis is only fragmentary. Previous work from our laboratory has shown that the breakdown of triglycerides (TG) is regulated in a cell cycle dependent manner, by activation of the Tgl4 lipase by the major cyclin-dependent kinase Cdc28. The lipases Tgl3 and Tgl4 are required for efficient cell cycle progression at the G1/S transition and their absence leads to a cell cycle delay (Kurat et al., Mol Cell 2009). We now show that defective lipolysis activates the Swe1 morphogenesis checkpoint kinase and halts cell cycle progression by phosphorylation of Cdc28 at tyrosine residue Y19. Saturated long-chain fatty acids and phytosphingosine supplementation rescue the cell cycle delay in lipase deficient strains, suggesting that Swe1 activity responds to an imbalanced sphingolipid metabolism, in the absence of TG degradation. 3. Compartmentalization of G1/S regulators allows signaling information to traverse a switch-like transition. Andreas Doncic, Jan M Skotheim. Department of Biology, Stanford university, Stanford, CA. The ability to specify and maintain discrete cell fates is essential for development. However, the dynamics underlying selection and stability of distinct cell types remain poorly understood. Previously, we provided a quantitative single-cell analysis of commitment dynamics during the mating-mitosis switch in budding yeast and showed that commitment to division corresponds precisely to activating the G1 cyclin positive feedback loop in competition with the cyclin inhibitor Far1. We showed that the coherent feed-forward regulation of the CDK inhibitor Far1 by the MAPK Fus3 integrates the pheromone signal to increase the stability of the pheromone-arrested state in response to a more persistent input signal. Here, we show how the decision to enter the cell cycle is enhanced by nuclear/cytoplasmic compartmentalization. Nuclear Far1 and Cln1/2 sets the point of commitment and the pool of nuclear Far1 is degraded before the cytoplasmic Far1 upon cell cycle entry. We show that the cytoplasmic pool of Far1 is stabilized in cycling cells exposed to low amounts of pheromone and thus provide daughter cells born in low pheromone conditions with a memory of the mother cell¹s pheromone exposure. Indeed, we find that cells inheriting more Far1 from their mother arrest longer. Thus, compartmentalization of similar pathway components allows distinct cytoplasmic and nuclear CDK thresholds that govern memory and decision-making functions respectively. 4. Coordination of cell cycle-regulated gene expression by Cdk1. Benjamin Landry, Claudine Mapa, Heather Arsenault, Kristin Poti, Jennifer Benanti. Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA. Accurate cell division depends upon the coordination of many cellular processes with the cell cycle. This coordination is achieved in part by the orchestrated expression of groups of genes that peak in different cell cycle phases. Cyclin- dependent kinase (Cdk1) plays a key role in regulating this cyclical gene expression, and it phosphorylates almost all cell cycle-regulatory transcription factors (TFs). However, the details of how phosphorylation modulates the functions of many cell cycle-regulatory TFs are not well understood. Here, we find that simultaneous elimination of Cdk1-mediated phosphorylation of four S-phase TFs delays mitotic progression and reduces fitness of budding yeast. Although cell cycle- regulated genes still cycle in the absence of phosphorylation, peak expression of many S and M/G1 phase genes decreases, indicating that Cdk1 modulates gene expression levels. Blocking phosphorylation interfered with SCF-mediated degradation and stabilized each of the four TFs. Consistent with these findings, blocking phosphorylation of the repressors Yox1 and Yhp1 led to increased chromatin association and decreased expression of target genes. Interestingly, we found that Cdk1 coordinated the activation and degradation of the activator Hcm1. Phosphorylation of the C-terminus of Hcm1 promoted its association with target gene promoters, whereas phosphorylation of the N-terminus promoted its degradation. Altogether, we conclude that Cdk1 promotes late cell cycle gene expression by both activating transcriptional activators and inactivating transcriptional repressors. Furthermore, our data suggest that coordinated regulation of the TF network by Cdk1 is necessary for faithful cell division. 5. Understanding the Regulation, Composition and Function of P bodies and Stress Granules in Quiescent Cells. Khyati H Shah, Paul K Herman. Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210. In response to stress, eukaryotic cells accumulate mRNAs and proteins at discrete sites in the cytoplasm. Two of the best characterized of these granules, P bodies (PBs) and Stress Granules (SGs), are differentially regulated as the cAMP- dependent protein kinase (PKA) specifically regulates the assembly of the former in S. cerevisiae. In addition, PBs form prior to stationary phase arrest and are important for the long-term survival of quiescent cells. In contrast, SGs are not assembled until after cells have entered stationary phase and thus may serve as an important marker for this quiescent state. These evolutionarily conserved ribonucleoprotein (RNP) structures may provide the cell with a dynamic mode of compartmentalization within the eukaryotic cytoplasm. To further understand the regulation and function of these RNP assemblies, we examined the localization of the entire set of S. cerevisiae protein kinases and phosphatases during the entry into stationary phase. Interestingly, ~20% of these enzymes were found to relocate to discrete cytoplasmic foci. The first three groups of localization patterns include enzymes that localize to either PBs or SGs specifically and those found at both types of granules in stationary phase cells. As with the core constituents, the localization to PBs was regulated by PKA activity and was dependent upon the presence
Load more

Recommended publications
  • 2020 Program Book
    PROGRAM BOOK Note that TAGC was cancelled and held online with a different schedule and program. This document serves as a record of the original program designed for the in-person meeting. April 22–26, 2020 Gaylord National Resort & Convention Center Metro Washington, DC TABLE OF CONTENTS About the GSA ........................................................................................................................................................ 3 Conference Organizers ...........................................................................................................................................4 General Information ...............................................................................................................................................7 Mobile App ....................................................................................................................................................7 Registration, Badges, and Pre-ordered T-shirts .............................................................................................7 Oral Presenters: Speaker Ready Room - Camellia 4.......................................................................................7 Poster Sessions and Exhibits - Prince George’s Exhibition Hall ......................................................................7 GSA Central - Booth 520 ................................................................................................................................8 Internet Access ..............................................................................................................................................8
    [Show full text]
  • The Development of Cancer Neochromosomes
    Cancer Cell Previews with regard to the precise localization of chemotherapy (Ma et al., 2013, 2014). T., Mignot, G., Ullrich, E., et al. (2009). Nat. Med. 15 DC subsets within the tumor bed. Broz Moreover, direct purification of intratu- , 1170–1178. + et al. (2014) found that both CD11b moral DC subsets yields functional tumor Hildner, K., Edelson, B.T., Purtha, W.E., Diamond, + DC1 and CD103 DC2 were preferentially antigen-presenting cells that are able to M., Matsushita, H., Kohyama, M., Calderon, B., located in collagen-rich zones distal to the prime naive T cells in vitro (Broz et al., Schraml, B.U., Unanue, E.R., Diamond, M.S., et al. (2008). Science 322, 1097–1100. tumor nodules where TAM1 and TAM2 2014) and elicit anticancer immune cells were found. In contrast, Ruffell response upon adoptive transfer in vivo Kroemer, G., Galluzzi, L., Kepp, O., and Zitvogel, L. et al. (2014) report that CD103+ cells (Ma et al., 2013). These results reinforce (2013). Annu. Rev. Immunol. 31, 51–72. were dispersed throughout the tumor the idea that the tumor may be considered Ma, Y., Adjemian, S., Mattarollo, S.R., Yamazaki, stroma in the proximity of macrophages. as a full-blown lymphoid organ, in which T., Aymeric, L., Yang, H., Portela Catani, J.P., Although Ruffell et al. (2014) found all steps of cellular immune responses Hannani, D., Duret, H., Steegh, K., et al. (2013). no change in the localization of CD103+ starting with appropriate presentation of Immunity 38, 729–741. cells after treatment with paclitaxel and tumor antigens by dendritic cells occur Ma, Y., Mattarollo, S.R., Adjemian, S., Yang, H., aCSF-1, Ma et al.
    [Show full text]
  • The Life History of Neochromosomes Revealed
    AUTHOR'S VIEW Molecular & Cellular Oncology 2:4, e1000698; October/November/December 2015; Published with license by Taylor & Francis Group, LLC The life history of neochromosomes revealed Anthony T Papenfuss1,2,3,4,* and David M Thomas2,5,6,* 1Bioinformatics Division; The Walter & Eliza Hall Institute of Medical Research; Parkville, Australia; 2Peter MacCallum Cancer Centre; East Melbourne, Australia; 3Department of Medical Biology; University of Melbourne; Melbourne, Australia; 4Sir Peter MacCallum Department of Oncology; University of Melbourne; Melbourne, Australia; 5The Kinghorn Cancer Centre, Garvan Institute of Medical Research; Sydney, Australia; 6University of New South Wales; Sydney, Australia Keywords: neochromosome, chromothripsis, breakage-fusionbridge mechanism, liposarcoma, cancer evolution, computational modelling Neochromosomes are a little-studied class of chromosome-scale mutations that drive some cancers. By sequencing isolated neochromosomes from liposarcomas, we recently defined their structure at single-nucleotide resolution and proposed a model for their life history. Here, we summarize that work, highlighting significant aspects and providing historical context and insight into the discovery process. Neochromosomes are giant extra chro- leads to the formation of a ring chromo- specialized method because of the unusual mosomes that are found in 3% of cancers some. During replication, DNA crossover nature of the complex data generated. overall1 but are particularly common in events between the sister chromatids can
    [Show full text]
  • An Evaluation of Cancer Subtypes and Glioma Stem Cell Characterisation Unifying Tumour Transcriptomic Features with Cell Line Expression and Chromatin Accessibility
    An evaluation of cancer subtypes and glioma stem cell characterisation Unifying tumour transcriptomic features with cell line expression and chromatin accessibility Ewan Roderick Johnstone EMBL-EBI, Darwin College University of Cambridge This dissertation is submitted for the degree of Doctor of Philosophy Darwin College December 2016 Dedicated to Klaudyna. Declaration • I hereby declare that except where specific reference is made to the work of others, the contents of this dissertation are original and have not been submitted in whole or in part for consideration for any other degree or qualification in this, or any other university. • This dissertation is my own work and contains nothing which is the outcome of work done in collaboration with others, except as specified in the text and Acknowledge- ments. • This dissertation is typeset in LATEX using one-and-a-half spacing, contains fewer than 60,000 words including appendices, footnotes, tables and equations and has fewer than 150 figures. Ewan Roderick Johnstone December 2016 Acknowledgements This work was funded by the Biotechnology and Biological Sciences Research Council (BBSRC, Ref:1112564) and supported by the European Molecular Biology Laboratory (EMBL) and its outstation, the European Bioinformatics Institute (EBI). I have many people to thank for assistance in preparing this thesis. First and foremost I must thank my supervisor, Paul Bertone for his support and willingness to take me on as a student. My thanks are also extended to present and past members of the Bertone group, particularly Pär Engström and Remco Loos who have provided a great deal of guidance over the course of my studentship.
    [Show full text]
  • Spatial Genome Organization As a Framework for Somatic Alterations in Human Cancer
    bioRxiv preprint doi: https://doi.org/10.1101/179176; this version posted August 22, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Spatial Genome Organization as a Framework for Somatic Alterations in Human Cancer Kadir C. Akdemir1, Yilong Li2, Roel G. Verhaak1,3, Rameen Beroukhim4, Peter Campbell2, Lynda Chin5 and P. Andrew Futreal1* on behalf of the PCAWG-Structural Variation Working Group 1 Genomic Medicine Department, MD Anderson Cancer Center, Houston, TX 77054. USA 2 Wellcome Trust Sanger Institute, Hinxton CB10 1SA, Cambridge, UK 3 Division of Computational Biology, The Jackson Laboratory for Genomic Medicine, Farmington, CT 06031, USA 4 Departments of Medical Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA, and Broad Institute, Cambridge, MA 02142, USA 5 Institute for Health Transformation, University of Texas, Houston, TX 77021, USA * Corresponding author ([email protected]) Genomic material within the nucleus is folded into successive layers in order to package and organize the long string of linear DNA. This hierarchical level of folding is closely associated with transcriptional regulation and DNA replication. Microscopic studies concluded that genome organization inside the nucleus is not random and chromosomes within the nucleus create territories1. More recent chromosome conformation studies have revealed that mammalian chromosomes are structured into tissue-invariant topologically associating domains (TADs) where the DNA within a given domain interacts more frequently together than with regions in other domains2,3.
    [Show full text]
  • Chromoanasynthesis Is a Common Mechanism That Leads to ERBB2
    Vasmatzis et al. BMC Cancer (2018) 18:738 https://doi.org/10.1186/s12885-018-4594-0 RESEARCHARTICLE Open Access Chromoanasynthesis is a common mechanism that leads to ERBB2 amplifications in a cohort of early stage HER2+ breast cancer samples George Vasmatzis1,2,3* , Xue Wang4, James B. Smadbeck1,2, Stephen J. Murphy1,2, Katherine B. Geiersbach5, Sarah H. Johnson1,2, Athanasios G. Gaitatzes1,2, Yan W. Asmann4, Farhad Kosari1,2, Mitesh J. Borad6, Daniel J. Serie1,2, Sarah A. McLaughlin7, Jennifer M. Kachergus8, Brian M. Necela8 and E. Aubrey Thompson9* Abstract Background: HER2 positive (HER2+) breast cancers involve chromosomal structural alterations that act as oncogenic driver events. Methods: We interrogated the genomic structure of 18 clinically-defined HER2+ breast tumors through integrated analysis of whole genome and transcriptome sequencing, coupled with clinical information. Results: ERBB2 overexpression in 15 of these tumors was associated with ERBB2 amplification due to chromoanasynthesis with six of them containing single events and the other nine exhibiting multiple events. Two of the more complex cases had adverse clinical outcomes. Chromosomes 8 was commonly involved in the same chromoanasynthesis with 17. In ten cases where chromosome 8 was involved we observed NRG1 fusions (two cases), NRG1 amplification (one case), FGFR1 amplification and ADAM32 or ADAM5 fusions. ERBB3 over-expression was associated with NRG1 fusions and EGFR and ERBB3 expressions were anti-correlated. Of the remaining three cases, one had a small duplication fully encompassing ERBB2 and was accompanied with a pathogenic mutation. Conclusion: Chromoanasynthesis involving chromosome 17 can lead to ERBB2 amplifications in HER2+ breast cancer.
    [Show full text]
  • Expression and Regulation of Scaffold Nucleoporins in Mammalian Cells
    Expression and regulation of scaffold nucleoporins in mammalian cells Leonor Leitão Marques Morais Thesis to obtain the Master Science Degree in Biological Engineering Supervisors: Doctor Valérie Doye Professor Gabriel António Amaro Monteiro Examination Committee Chairperson: Professor Duarte Miguel De França Teixeira dos Prazeres Supervisor: Professor Gabriel António Amaro Monteiro Member of the Committee: Professor Arsénio do Carmo Sales Mendes Fialho November 2018 Acknowledgements I would like to thank Valérie Doye for hosting me at her laboratory, at Institut Jacques Monod of the Université Paris Diderot, for contributing to my training as a researcher and for guiding me and helping me throughout the project. I also would like to thank Stéphanie Bolhy, one of Valérie’s team members, for nicely training, guiding and helping me, particularly on the technical level, so I could have the minimal requirement to do my technical work. Finally, I would like to thank the rest of Valérie’s team members, Alessandro Berto, Alba Gonzalez Estevez, Stéphane Pelletier and Annalisa Verrico, for always being available on helping me in any matter related to my training. i Abstract Nuclear pore complexes (NPCs) are large macromolecular structures embedded into the doubled- membrane nuclear envelope that form a channel, mediating the bidirectional nucleocytoplasmic transport. NPCs are built from multiple copies of around 30 different nuclear pore proteins called nucleoporins (NUPs). Over the years, nucleoporins have been linked to a multitude of cancers through chromosomal translocations generating fusion proteins, single point mutations, and changes in protein expression levels. In particular, the nucleoporin NUP107 gene has been recently shown to be amplified and overexpressed in well- and dedifferentiated liposarcoma (WD/DDLPS) that carry neochromosomes.
    [Show full text]
  • Patterns and Mechanisms of Structural Variations in Human Cancer Kijong Yi1 and Young Seok Ju 1
    Yi and Ju Experimental & Molecular Medicine (2018) 50:98 DOI 10.1038/s12276-018-0112-3 Experimental & Molecular Medicine REVIEW ARTICLE Open Access Patterns and mechanisms of structural variations in human cancer Kijong Yi1 and Young Seok Ju 1 Abstract Next-generation sequencing technology has enabled the comprehensive detection of genomic alterations in human somatic cells, including point mutations, chromosomal rearrangements, and structural variations (SVs). Using sophisticated bioinformatics algorithms, unbiased catalogs of SVs are emerging from thousands of human cancer genomes for the first time. Via careful examination of SV breakpoints at single-nucleotide resolution as well as local DNA copy number changes, diverse patterns of genomic rearrangements are being revealed. These “SV signatures” provide deep insight into the mutational processes that have shaped genome changes in human somatic cells. This review summarizes the characteristics of recently identified complex SVs, including chromothripsis, chromoplexy, microhomology-mediated breakage-induced replication (MMBIR), and others, to provide a holistic snapshot of the current knowledge on genomic rearrangements in somatic cells. Introduction alterations. Although there is no rule that clearly distin- Cancer genomics has contributed to medical oncology guishes the “small” and “large” variation categories, 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; by providing the genomic landscape and catalog of researchers currently regard 50 bp as the tentative cutoff somatic mutations of human cancers. This information criteria2. Before the era of whole-genome sequencing holds clinically actionable targets that may be used for (WGS), tentatively regarded as prior to 2010, the com- personalized oncology and the development of new prehensive detection of SV “breakpoints” (qualitative therapeutics. In addition, because the catalog of somatic changes) was not feasible in cancer genomes.
    [Show full text]
  • The Architecture and Evolution of Cancer Neochromosomes
    Cancer Cell Article The Architecture and Evolution of Cancer Neochromosomes Dale W. Garsed,1,8,9,15 Owen J. Marshall,5,15,17 Vincent D.A. Corbin,2,3,13,15 Arthur Hsu,2,15 Leon Di Stefano,2 Jan Schro¨ der,2,3 Jason Li,1 Zhi-Ping Feng,2,3 Bo W. Kim,5 Mark Kowarsky,2 Ben Lansdell,2 Ross Brookwell,6 Ola Myklebost,10 Leonardo Meza-Zepeda,10 Andrew J. Holloway,1 Florence Pedeutour,7 K.H. Andy Choo,5 Michael A. Damore,11 Andrew J. Deans,12 Anthony T. Papenfuss,2,3,4,8,13,16,* and David M. Thomas1,8,14,16,* 1Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia 2Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia 3Department of Medical Biology, University of Melbourne, VIC 3010, Australia 4Department of Mathematics and Statistics, University of Melbourne, VIC, 3010, Australia 5Chromosome Research, Murdoch Childrens Research Institute, and Department of Paediatrics, Royal Children’s Hospital, University of Melbourne, Parkville, VIC 3052, Australia 6Sullivan Nicolaides Pathology, Indooroopilly, QLD 4068, Australia 7Laboratory of Solid Tumors Genetics, Nice University Hospital, Nice 06107, France 8Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC 3010, Australia 9Department of Pathology, University of Melbourne, VIC 3010, Australia 10Department of Tumor Biology, Oslo University Hospital, Norwegian Radium Hospital, Oslo 0424, Norway 11Amgen, Thousand Oaks, CA 91320, USA 12St Vincent’s Institute, Fitzroy, VIC 3065, Australia 13Bioinformatics
    [Show full text]
  • Optical Mapping Reveals a Higher Level of Genomic Architecture of Chained Fusions in Cancer
    Downloaded from genome.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press Method Optical mapping reveals a higher level of genomic architecture of chained fusions in cancer Eva K.F. Chan,1,2,12 Daniel L. Cameron,3,4 Desiree C. Petersen,1,2 Ruth J. Lyons,1 Benedetta F. Baldi,1 Anthony T. Papenfuss,3,4,5,6,7 David M. Thomas,8,9 and Vanessa M. Hayes1,2,10,11,12 1Genomics and Epigenetics Division, Garvan Institute of Medical Research, New South Wales 2010, Australia; 2St Vincent’s Clinical School, University of New South Wales, New South Wales 2052, Australia; 3Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3052, Australia; 4Department of Medical Biology, University of Melbourne, Victoria 3010, Australia; 5Department of Mathematics and Statistics, University of Melbourne, Victoria 3010, Australia; 6Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria 3010, Australia; 7Bioinformatics and Cancer Genomics, Peter MacCallum Cancer Centre, Victoria 3002, Australia; 8The Kinghorn Cancer Centre, Garvan Institute of Medical Research, New South Wales 2010, Australia; 9Cancer Division, Garvan Institute of Medical Research, New South Wales 2010, Australia; 10School of Health Systems and Public Health, University of Pretoria, Hatfield 0002, South Africa; 11Central Clinical School, University of Sydney, New South Wales 2006, Australia Genomic rearrangements are common in cancer, with demonstrated links to disease progression and treatment response. These rearrangements can be complex, resulting in fusions of multiple chromosomal fragments and generation of derivative chromosomes. Although methods exist for detecting individual fusions, they are generally unable to reconstruct complex chained events.
    [Show full text]
  • 1 Minimally Invasive Surgery for Neurogenic Tumors of The
    1 Minimally Invasive Surgery for Neurogenic Tumors of The Posterior Mediastinum in Children Diana Rybakova1, Anatoly Kazanchzev1, Polad Kerimov1 1FGBU "NMIC Oncologists Them. N.n. Blokhin »moscow, Ministry of Health of The Russian Federation, Moscow, Moscow, Russian Federation Actuality: Neurogenic tumors of the mediastinum in children occur in 15% of all tumors of the nervous system. The main method of treatment of this pathology is surgery, including minimally invasive surgery. Objectives: To determine the possibility of minimally invasive surgery in the treatment of neurogenic tumors of the posterior mediastinum in children. Materials and methods: From 2007 to 2016, 47 patients underwent thoracoscopic operations of the neurogenic tumor of the mediastinum. The age of the patients varied from 5 months to 16 years. The largest number of children entered the group from 1 year to 3 years - 18 people (38.3%). The sex ratio was approximately equal to: boys were 24 (51%), girls - 23 (49%).The duration of the operations was, on average, 49 minutes. In 85% of cases, the operation time was less than 60 minutes, and only 15% more than 1 hour. The blood loss during thoracoscopic operations averaged 14.3 ml. In 36 cases, blood loss was not observed. No intraoperative complications were noted. All patients within the first 24 hours after the operation were transferred to the profile department from the intensive care unit. Postoperative complications arose in 4 patients - Horner's syndrome, in connection with the localization of the tumor process in the apical part of the chest. 43 patients after surgery were in the surgical clinic for no more than 3 days, and 4 patients were detained in the hospital for up to 7 days to assess the neurological status due to manifestations of Horner's syndrome.
    [Show full text]
  • Small Ring Has Big Potential: Insights Into Extrachromosomal DNA in Cancer Yihao Wang1,2, Rui Huang1,2, Guopei Zheng1,2 and Jianfeng Shen1,2*
    Wang et al. Cancer Cell Int (2021) 21:236 https://doi.org/10.1186/s12935-021-01936-6 Cancer Cell International REVIEW Open Access Small ring has big potential: insights into extrachromosomal DNA in cancer Yihao Wang1,2, Rui Huang1,2, Guopei Zheng1,2 and Jianfeng Shen1,2* Abstract Recent technical advances have led to the discovery of novel functions of extrachromosomal DNA (ecDNA) in mul- tiple cancer types. Studies have revealed that cancer-associated ecDNA shows a unique circular shape and contains oncogenes that are more frequently amplifed than that in linear chromatin DNA. Importantly, the ecDNA-mediated amplifcation of oncogenes was frequently found in most cancers but rare in normal tissues. Multiple reports have shown that ecDNA has a profound impact on oncogene activation, genomic instability, drug sensitivity, tumor heterogeneity and tumor immunology, therefore may ofer the potential for cancer diagnosis and therapeutics. Nevertheless, the underlying mechanisms and future applications of ecDNA remain to be determined. In this review, we summarize the basic concepts, biological functions and molecular mechanisms of ecDNA. We also provide novel insights into the fundamental role of ecDNA in cancer. Keywords: EcDNA, Oncogene amplifcation, Chromosomal rearrangement, Epigenetic modifcation, Tumor heterogeneity Introduction ecDNA that is rarely seen in normal cells, eccDNA is pre- Extrachromosomal DNA (ecDNA) is a particular type sent in both normal cells and cancer cells, and eccDNA of DNA molecule outside of the chromosome that is may promote tumorigenesis through the selection of usually 1–3 Mb in length [1]. EcDNA does not contain telomere extension and modulation of genomic instabil- centromeres or telomeres, but it has regulatory regions ity [10, 11].
    [Show full text]