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Supplement 1 Microarray Studies

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EASE Categories Significantly Enriched in vs MG vs vs MGC4-2 Pt1-C vs C4-2 Pt1-C UP-Regulated Genes MG System Gene Category EASE Global MGRWV Pt1-N RWV Pt1-N Score FDR GO Molecular Extracellular matrix cellular construction 0.0008 0 110 genes up- Function Interpro EGF-like domain 0.0009 0 regulated GO Molecular Oxidoreductase activity\ acting on single dono 0.0015 0 Function GO Molecular Calcium ion binding 0.0018 0 Function Interpro Laminin-G domain 0.0025 0 GO Biological Process Cell Adhesion 0.0045 0 Interpro Collagen Triple helix repeat 0.0047 0 KEGG pathway Complement and coagulation cascades 0.0053 0 KEGG pathway Immune System – Homo sapiens 0.0053 0 Interpro Fibrillar collagen C-terminal domain 0.0062 0 Interpro Calcium-binding EGF-like domain 0.0077 0 GO Molecular Cell adhesion molecule activity 0.0105 0 Function EASE Categories Significantly Enriched in Down-Regulated Genes System Gene Category EASE Global Score FDR GO Biological Process Copper ion homeostasis 2.5E-09 0 Interpro Metallothionein 6.1E-08 0 Interpro Vertebrate metallothionein, Family 1 6.1E-08 0 GO Biological Process Transition metal ion homeostasis 8.5E-08 0 GO Biological Process Heavy metal sensitivity/resistance 1.9E-07 0 GO Biological Process Di-, tri-valent inorganic cation homeostasis 6.3E-07 0 GO Biological Process Metal ion homeostasis 6.3E-07 0 GO Biological Process Cation homeostasis 2.1E-06 0 GO Biological Process Cell ion homeostasis 2.1E-06 0 GO Biological Process Ion homeostasis 2.1E-06 0 GO Molecular Helicase activity 2.3E-06 0 Function GO Biological Process Cell homeostasis 4.6E-06 0 GO Biological Process Homeostasis 5.5E-06 0 GO Molecular Cadmium ion binding 0.0002 0 Function GO Molecular Copper/cadmium binding 0.0002 0 Function GO Molecular Zinc ion binding 0.0004 0 Function GO Biological Process DNA replication initiation 0.0008 0 GenMAPP pathway Hs_Cell cycle 0.0008 0 GO Biological Process Cell growth and/or maintenance 0.0009 0 KEGG pathway Cell cycle – Homo sapiens 0.0011 0 GO Biological Process DNA replication 0.0018 0 GO Biological Process Mitotic cell cycle 0.0018 0 GO Biological Process S phase of mitotic cell cycle 0.0020 0 KEGG pathway Cell growth and Death – Homo Sapiens 0.0031 0 GO Molecular Binding 0.0043 0 Function GO Biological Process Obsolete biological process 0.0049 0 54 genes down- GO Molecular Catalytic activity 0.0129 0 Function regulated GO Biological Process Cell cycle 0.0139 0 GO Biological Process Regulation of cell cycle 0.0190 0 GO Biological Process Cell proliferation 0.0198 0 4985 unique 164 common GO Molecular Purine nucleotide binding 0.0226 0 Function genes genes GO Molecular Nucleotide binding 0.0237 0 TABLE 1.Genes Up-Regulated in Both MGC4-2 and PTC with 1-Sample T-Test q-value <10% ENTREZ AVE FOLD ENTREZ AVE FOLD HUGO NAME GENBANK GENE ¨ HUGO NAME GENBANK GENE ¨ DNA SYNTHESIS / TRANSCRIPTION REGULATION / DNA REPAIR SIGNAL TRANSDUCTION RFX5 Regulatory factor X 5 (influences HLA class II expression) AA418045 5993 1.8 DKK1 Dickkopf homolog 1 (Xenopus laevis) AA253464 22943 3.4 FLJ11196 La ribonucleoprotein domain family member 6 AA130193 55323 1.6 DUSP6 Dual specificity phosphatase 6 AA630374 1848 1.8 CYLN2 Cytoplasmic linker 2 H15662 7461 1.6 SSB1 SplA/ryanodine receptor domain and SOCS box containing 1 T97925 80176 1.6 HIST1H2AC Histone 1 H2ac N50797 8334 1.5 FZD8 Frizzled homolog 8 (Drosophila) AA457138 8325 1.5 SSX2IP Synovial sarcoma X breakpoint 2 interacting protein H20847 117178 1.5 PSD3 Pleckstrin and Sec7 domain containing 3 AA460826 23362 1.5 JMY Junction-mediating and regulatory protein AA608739 133746 1.5 FURIN Furin (paired basic amino acid cleaving enzyme) AA856874 5045 1.5 TUSC3 Tumor suppressor candidate 3 N66008 7991 1.4 SOCS5 Suppressor of cytokine signaling 5 N90775 9655 1.4 CALR Calreticulin H99170 811 1.4 MAPK1 Mitogen-activated protein kinase 1 AA683077 5594 1.4 U2AF2 U2 (RNU2) small nuclear RNA auxiliary factor 2 AA405748 11338 1.4 ADAM10 ADAM metallopeptidase domain 10 AA043347 102 1.4 JUNB Jun B proto-oncogene T99236 3726 1.4 TRIO Triple functional domain (PTPRF interacting) AA487480 7204 1.4 LMO4 LIM domain only 4 H27986 8543 1.4 EPS8 Epidermal growth factor receptor pathway substrate 8 H13623 2059 1.3 HIS1 Hexamethylene bis-acetamide inducible 1 W68585 10614 1.4 STRUCTURAL / ADHESION / MOTILITY ETV5 Ets variant gene 5 (ets-related molecule) AA460265 2119 1.4 CDH6 Cadherin 6 type 2 K-cadherin (fetal kidney) AA421819 1004 3.6 SNAI2 Snail homolog 2 (Drosophila) H57310 6591 1.3 KRTHA4 Keratin hair acidic 4 W49755 | AA28 3885 2.6 CTDSP2 CTD (carboxy-terminal domain RNA polymerase II polypeptide A) small phos AA404264 10106 1.3 TNC Tenascin C (hexabrachion) R39239 3371 2.2 PRRG2 Proline rich Gla (G-carboxyglutamic acid) 2 AA430552 5639 1.3 COL5A2 Collagen type V alpha 2 AA461456 1290 2.0 GROWTH / DIFFERENTIATION / APOPTOSIS COL12A1 Collagen type XII alpha 1 AA478481 1303 1.9 ANXA4 Annexin A4 AA419015 307 1.8 FBLN2 Fibulin 2 AA452840 2199 1.9 STK38L Serine/threonine kinase 38 like AA148542 23012 1.7 ALCAM Activated leukocyte cell adhesion molecule R39862 214 1.9 TM4SF10 Transmembrane protein 47 N52772 83604 1.7 COL5A1 Collagen type V alpha 1 R75635 1289 1.8 MAP3K8 Mitogen-activated protein kinase kinase kinase 8 W56266 1326 1.6 TIMP3 TIMP metallopeptidase inhibitor 3 (Sorsby fundus dystrophy pseudoinflammaAA099153 7078 1.7 RARRES3 Retinoic acid receptor responder (tazarotene induced) 3 W47350 5920 1.6 AGRN Agrin AA458878 375790 1.7 BNIP3L BCL2/adenovirus E1B 19kDa interacting protein 3-like AA025112 665 1.6 COL3A1 Collagen type III alpha 1 (Ehlers-Danlos syndrome type IV autosomal dominaT98612 1281 1.6 PLK2 Polo-like kinase 2 (Drosophila) AA460152 10769 1.4 CKB Creatine kinase brain AA894557 1152 1.6 VMP1 Transmembrane protein 49 AA485373 81671 1.4 CNN3 Calponin 3 acidic AA043228 1266 1.6 FHL1 Four and a half LIM domains 1 AA455925 2273 1.4 DCBLD2 Discoidin CUB and LCCL domain containing 2 AA431438 131566 1.5 PINK1 PTEN induced putative kinase 1 AA412184 65018 1.3 CDC42EP3 CDC42 effector protein (Rho GTPase binding) 3 AA115248 10602 1.5 RAF1 V-raf-1 murine leukemia viral oncogene homolog 1 N25425 5894 1.3 C9orf13 Sushi von Willebrand factor type A EGF and pentraxin domain containing 1 AA424560 79987 1.5 GSPT1 G1 to S phase transition 1 R93719 2935 1.3 CLDN11 Claudin 11 (oligodendrocyte transmembrane protein) AA443966 5010 1.5 IMMUNE / INFAMMATORY / STRESS RESPONSE SPARC Secreted protein acidic cysteine-rich (osteonectin) H95960 6678 1.4 DAF Decay accelerating factor for complement (CD55 Cromer blood group systemR09561 1604 1.7 SDC4 Syndecan 4 (amphiglycan ryudocan) AA148737 6385 1.4 G1P3 Interferon alpha-inducible protein (clone IFI-6-16) AA448478 2537 1.6 KAL1 Kallmann syndrome 1 sequence H17883 3730 1.4 B7H3 CD276 antigen N54338 80381 1.5 HSPG2 Heparan sulfate proteoglycan 2 (perlecan) AA427561 3339 1.4 THY1 Thy-1 cell surface antigen AA496283 7070 1.5 THBS2 Thrombospondin 2 H38240 7058 1.4 CD81 CD81 antigen (target of antiproliferative antibody 1) AA486556 975 1.4 CSPG2 Chondroitin sulfate proteoglycan 2 (versican) AA101875 1462 1.4 PROS1 Protein S (alpha) T74192 5627 1.4 PTPRS Protein tyrosine phosphatase receptor type S AA137072 5802 1.4 MCP Membrane cofactor protein (CD46 trophoblast-lymphocyte cross-reactive ant AA463497 4179 1.3 TRANSLATION - PROTEIN SYNTHESIS CD59 CD59 antigen p18-20 (antigen identified by monoclonal antibodies 163A5 EJ H60549 966 1.3 EIF2B3 Eukaryotic translation initiation factor 2B subunit 3 gamma 58kDa W58368 8891 2.5 METABOLISM - CARBOHYDRATE PLOD2 Procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 H99816 5352 1.6 XYLT1 Hypothetical protein LOC283824 R56916 64131 1.6 PLOD1 Procollagen-lysine 1 2-oxoglutarate 5-dioxygenase 1 AA476241 5351 1.5 KIAA0746 KIAA0746 protein AA456569 23231 1.6 PDIR Protein disulfide isomerase family A member 5 AA404387 10954 1.5 TKT Transketolase (Wernicke-Korsakoff syndrome) AA070358 7086 1.4 GOLPH2 Golgi phosphoprotein 2 AA454597 51280 1.4 MGAT3 Mannosyl (beta-14-)-glycoprotein beta-14-N-acetylglucosaminyltransferase AA421473 4248 1.3 EIF1AY Eukaryotic translation initiation factor 1A Y-linked AA047039 9086 1.3 GAA Glucosidase alpha acid (Pompe disease glycogen storage disease type II) AA444009 2548 1.3 CPEB2 Cytoplasmic polyadenylation element binding protein 2 N36923 132864 1.3 METABOLISM - LIPID/STEROL PTGFRN Prostaglandin F2 receptor negative regulator AA427887 5738 1.3 PTGS2 Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cycR80217 5743 2.3 PPIB Peptidylprolyl isomerase B (cyclophilin B) N45313 5479 1.2 ALDH3B2 Aldehyde dehydrogenase 3 family member B2 AA443630 222 1.8 TRANSPORT/TRAFFICKING ALOX5 Arachidonate 5-lipoxygenase H51574 240 1.7 FABP5 Fatty acid binding protein 5 (psoriasis-associated) N47717 2171 1.9 SCD Stearoyl-CoA desaturase (delta-9-desaturase) AA457700 6319 1.7 CRABP2 Cellular retinoic acid binding protein 2 AA598508 1382 1.9 HMGCS1 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (soluble) T56013 3157 1.6 KCNK1 Potassium channel subfamily K member 1 N62620 3775 1.6 METABOLISM - PROTEIN SEC24D SEC24 related gene family member D (S cerevisiae) AA449107 9871 1.5 ASS Argininosuccinate synthetase AA676466 445 1.4 SNX1 Sorting nexin 1 AA410893 6642 1.4 P4HA1 Procollagen-proline 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase) alpAA457671 5033 1.3 KIAA0515 KIAA0515 AA481143 84726 1.4 METABOLISM - OTHER SLC16A1 AKR7 family pseudogene AA043133 6566 1.3 RDH10 Retinol dehydrogenase 10 (all-trans) AA449821 157506 2.2 SEC13L1 SEC13-like 1 (S cerevisiae) AA496784 6396 1.2 EDEM1 ER degradation
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    Published OnlineFirst April 8, 2020; DOI: 10.1158/2159-8290.CD-19-0532 RESEARCH ARTICLE Gain-of-Function Genetic Alterations of G9a Drive Oncogenesis Shinichiro Kato 1 , Qing Yu Weng 1 , Megan L. Insco 2 , 3 , 4 , Kevin Y. Chen 2 , 3 , 4 , Sathya Muralidhar 5 , Joanna Pozniak 5 , Joey Mark S. Diaz5 , Yotam Drier 6 , 7 , 8 , Nhu Nguyen 1 , Jennifer A. Lo 1 , Ellen van Rooijen 2 , 3 , Lajos V. Kemeny 1 , Yao Zhan1 , Yang Feng 1 , Whitney Silkworth 1 , C. Thomas Powell 1 , Brian B. Liau 9 , Yan Xiong 10 , Jian Jin 10 , Julia Newton-Bishop5 , Leonard I. Zon 2 , 3 , Bradley E. Bernstein 6 , 7 , 8 , and David E. Fisher 1 . Downloaded from cancerdiscovery.aacrjournals.org on September 25, 2021. © 2020 American Association for Cancer Research. Published OnlineFirst April 8, 2020; DOI: 10.1158/2159-8290.CD-19-0532 ABSTRACT Epigenetic regulators, when genomically altered, may become driver oncogenes that mediate otherwise unexplained pro-oncogenic changes lacking a clear genetic stimulus, such as activation of the WNT/β -catenin pathway in melanoma. This study identifi es previ- ously unrecognized recurrent activating mutations in the G9a histone methyltransferase gene, as well as G9a genomic copy gains in approximately 26% of human melanomas, which collectively drive tumor growth and an immunologically sterile microenvironment beyond melanoma. Furthermore, the WNT pathway is identifi ed as a key tumorigenic target of G9a gain-of-function, via suppression of the WNT antagonist DKK1. Importantly, genetic or pharmacologic suppression of mutated or amplifi ed G9a using multiple in vitro and in vivo models demonstrates that G9a is a druggable target for therapeutic intervention in melanoma and other cancers harboring G9a genomic aberrations.
  • Blood Vitronectin Is a Major Activator of LIF and IL-6 in the Brain Through Integrin–FAK and Upar Signaling Matthew P

    Blood Vitronectin Is a Major Activator of LIF and IL-6 in the Brain Through Integrin–FAK and Upar Signaling Matthew P

    © 2018. Published by The Company of Biologists Ltd | Journal of Cell Science (2018) 131, jcs202580. doi:10.1242/jcs.202580 RESEARCH ARTICLE Blood vitronectin is a major activator of LIF and IL-6 in the brain through integrin–FAK and uPAR signaling Matthew P. Keasey1, Cuihong Jia1, Lylyan F. Pimentel1,2, Richard R. Sante1, Chiharu Lovins1 and Theo Hagg1,* ABSTRACT Microglia and astrocytes express the VTN receptors αvβ3 and α β We defined how blood-derived vitronectin (VTN) rapidly and potently v 5 integrin (Herrera-Molina et al., 2012; Kang et al., 2008; activates leukemia inhibitory factor (LIF) and pro-inflammatory Milner, 2009; Welser-Alves et al., 2011). Microglia and astrocytes, interleukin 6 (IL-6) in vitro and after vascular injury in the brain. as well as endothelial cells, are major producers of pro- α in vitro Treatment with VTN (but not fibrinogen, fibronectin, laminin-111 or inflammatory cytokines, such as IL-6 and TNF , and collagen-I) substantially increased LIF and IL-6 within 4 h in after traumatic or ischemic injury to the brain (Banner et al., 1997; C6-astroglioma cells, while VTN−/− mouse plasma was less effective Erta et al., 2012; Lau and Yu, 2001) or upon self-induction by IL-6 than that from wild-type mice. LIF and IL-6 were induced by (Van Wagoner and Benveniste, 1999). IL-6 is a major regulator of a intracerebral injection of recombinant human (rh)VTN in mice, but variety of inflammatory disorders and a target for therapies (Hunter induction seen upon intracerebral hemorrhage was less in VTN−/− and Jones, 2015).
  • Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?

    Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?

    Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement.