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network_name_str Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str 2135
spelling Acuna-Hidalgo, RocioDeriziotis, PelagiaSteehouwer, MarloesGilissen, ChristianGraham, Sarah A.van Dam, SipkoHoover-Fong, JulieTelegrafi, Aida B.Destree, AnneSmigiel, RobertLambie, Lindsday A.Kayserili, HülyaAltunoglu, UmutLapi, ElisabettaUzielli, Maria LuisaAracena, MarianaNur, Banu G.Mihci, ErcanMoreira, Lilia M. A.Borges Ferreira, VivianeHorovitz, Dafne Dain GandelmanRocha, Katia M. daJezela-Stanek, AleksandraBrooks, Alice S.Reutter, HeikoCohen, Julie S.Fatemi, AliSmitka, MartinGrebe, Theresa A.Di Donato, NataliyaDeshpande, CharuVandersteen, AnthonyMarques Lourenço, CharlesDufke, AndreasRossier, EvaAndre, GwenaelleBaumer, AlessandraSpencer, CareniMcGaughran, JulieFranke, LudeVeltman, Joris A.De Vries, Bert B. A.Schinzel, AlbertFisher, Simon E.Hoischen, Alexandervan Bon, Bregje W.2021-01-06T19:42:43Z2021-01-06T19:42:43Z2017Acuna-Hidalgo R, Deriziotis P, Steehouwer M, Gilissen C, Graham SA, van Dam S, Hoover-Fong J, Telegrafi AB, Destree A, Smigiel R, Lambie LA, Kayserili H, Altunoglu U, Lapi E, Uzielli ML, Aracena M, Nur BG, Mihci E, Moreira LM, Borges Ferreira V, Horovitz DD, da Rocha KM, Jezela-Stanek A, Brooks AS, Reutter H, Cohen JS, Fatemi A, Smitka M, Grebe TA, Di Donato N, Deshpande C, Vandersteen A, Marques Lourenço C, Dufke A, Rossier E, Andre G, Baumer A, Spencer C, McGaughran J, Franke L, Veltman JA, De Vries BB, Schinzel A, Fisher SE, Hoischen A, van Bon BW. Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies. PLoS Genet. 2017 Mar 27;13(3):e1006683. doi: 10.1371/journal.pgen.1006683. PMID: 28346496; PMCID: PMC5386295.1553-7390https://www.arca.fiocruz.br/handle/icict/4551810.1371/journal.pgen.1006683engPublic Library of Science [Commercial Publisher]Abnormalities, Multiple / geneticsAbnormalities, Multiple / metabolismAbnormalities, Multiple / pathologyBlotting, WesternCarrier Proteins / geneticsCarrier Proteins / metabolismCell LineCell Proliferation / geneticsCell Transformation, Neoplastic / geneticsChildChild, PreschoolCraniofacial Abnormalities / geneticsCraniofacial Abnormalities / metabolismCraniofacial Abnormalities / pathologyFemaleGene Expression ProfilingGenetic Association StudiesGenetic Predisposition to Disease / geneticsGerm-Line MutationHEK293 CellsHand Deformities, Congenital / geneticsHand Deformities, Congenital / metabolismHand Deformities, Congenital / pathologyHematologic Neoplasms / geneticsPhenotypeNuclear Proteins / metabolismHematologic Neoplasms / metabolismHematologic Neoplasms / pathologyNuclear Proteins / geneticsNails, Malformed / pathologyNails, Malformed / metabolismNails, Malformed / geneticsMutationMaleHumansInfantIntellectual Disability / pathologyIntellectual Disability / geneticsInfant, NewbornOverlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignanciesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleRadboud University Medical Center. Radboud Institute of Molecular Life Sciences. Department of Human Genetics. Nijmegen. The Netherlands.Max Planck Institute for Psycholinguistics. Language and Genetics Department. Nijmegen. The Netherlands.Radboud University Medical Center. Radboud Institute of Molecular Life Sciences. Department of Human Genetics. Nijmegen. The Netherlands.Radboud University Medical Center. Radboud Institute of Molecular Life Sciences. Department of Human Genetics. Nijmegen. The Netherlands. / Radboud University Medical Center. Donders Centre for Neuroscience. Department of Human Genetics. Nijmegen. The Netherlands.Max Planck Institute for Psycholinguistics. Language and Genetics Department. Nijmegen. The Netherlands.University of Groningen. University Medical Center Groningen. Department of Genetics. Groningen. the Netherlands.Johns Hopkins University. McKusick-Nathans Institute of Genetic Medicine. Baltimore, Maryland. USAGeneDx. Gaithersburg. Baltimore, Maryland. USAInstitute of Pathology and Genetics. Gosselies. Belgium.Medical University. Department of Pediatrics and Rare Disorders. Wroclaw. Poland.University of the Witwatersrand. Faculty of Health Sciences. National Health Laboratory Service and School of Pathology. Division of Human Genetics. Johannesburg. South Africa.Koç University School of Medicine. Medical Genetics Department. İstanbul. Turkey.İstanbul University. İstanbul Medical Faculty. Medical Genetics Department. İstanbul, Turkey.Anna Meyer Children's University Hospital. Medical Genetics Unit. Florence. Italy.University of Florence. Genetic Science. Firenze. ItalyPontificia Universidad Católica de Chile. División de Pediatría. / Hospital Dr. Luis Calvo Mackenna. Unidad de Genética. Santiago. Chile.Akdeniz University Medical School. Department of Pediatric Genetics. Antalya. Turkey.Universidade Federal da Bahia. Instituto de Biologia. Laboratório de Genética Humana. Bahia. Brasil.Hospital Santa Izabel. Salvador, BA. Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Centro de Genética Médica. Rio de Janeiro, RJ, BrasilUniversidade de São Paulo. Instituto de Biociência. Centro de Estudos de Genoma Humano, São Paulo, SP. Brasil.Children's Memorial Health Institute. Department of Medical Genetics. Warsaw. Poland.Sophia Children's Hospital. Department of Clinical Genetics. Erasmus MC, Rotterdam. The Netherlands.University of Bonn. Institute of Human Genetics. Bonn. Germany / University of Bonn. Children's Hospital. Department of Neonatology and Pediatric Intensive Care. Bonn. Germany.The Johns Hopkins Hospital. Kennedy Krieger Institute. Departments of Neurology and Pediatrics. Division of Neurogenetics. Baltimore, Maryland. USATechnische Universität Dresden. Medizinische Fakultät Carl Gustav Carus. Abteilung Neuropädiatrie. Germany.Phoenix Children's Hospital. Division of Genetics & Metabolism. Phoenix, Arizona. USA.Institute for Clinical Genetics. TU Dresden. Dresden. Germany.Guy's and St. Thomas' NHS Foundation Trust. Department of Genetics. London. United Kingdom.Kennedy Galton Centre. North West Thames Regional Genetics Unit. North West, London. UK / Hospitals NHS Trust. Northwick Park & St Marks Hospital. Harrow, Middlesex. UK.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Genética Médica. Unidade de Neurogenética. São Paulo, SP. Brasil.University of Tübingen. Institute of Medical Genetics and Applied Genomics. Tübingen. Germany.University of Tübingen. Institute of Medical Genetics and Applied Genomics. Tübingen. Germany.Hôpital Pellegrin. Unité de foetopathologie. Bordeaux. FranceUniversity of Zurich. Institute of Medical Genetics. Schlieren. Switzerland.University of the Witwatersrand. Faculty of Health Sciences. National Health Laboratory Service and School of Pathology. Division of Human Genetics. Johannesburg. South Africa.The University of Queensland.Queensland and School of Medicine. Genetic Health Queensland. Royal Brisbane and Women's Hospital. Brisbane, Queensland. Australia.University of Groningen. University Medical Center Groningen. Department of Genetics. Groningen. the Netherlands.Radboud University Medical Center. Radboud Institute of Molecular Life Sciences. Department of Human Genetics. Nijmegen. The Netherlands. / Newcastle University. Institute of Genetic Medicine, International Centre for Life. Newcastle upon Tyne. United Kingdom.Radboud University Medical Center. Radboud Institute of Molecular Life Sciences. Department of Human Genetics. Nijmegen. The Netherlands./ Radboud University Medical Center. Donders Centre for Neuroscience. Department of Human Genetics. Nijmegen. The Netherlands.Radboud University Medical Center. Radboud Institute of Molecular Life Sciences. Department of Human Genetics. Nijmegen. The Netherlands. / Radboud University Medical Center. Donders Centre for Neuroscience. Department of Human Genetics. Nijmegen. The Netherlands.Radboud University Medical Center. Radboud Institute of Molecular Life Sciences. Department of Human Genetics. Nijmegen. The Netherlands. / Radboud University Medical Center.Donders Centre for Neuroscience. Department of Human Genetics. Nijmegen. The Netherlands.University of Zurich. Institute of Medical Genetics. Schlieren. Switzerland.Max Planck Institute for Psycholinguistics. Language and Genetics Department. Nijmegen. The Netherlands. / Radboud University. Donders Institute for Brain, Cognition and Behaviour. Nijmegen. The Netherlands.Radboud University Medical Center. Radboud Institute of Molecular Life Sciences. Department of Human Genetics. Nijmegen. The Netherlands. / Radboud University Medical Center. Donders Centre for Neuroscience. Department of Human Genetics. Nijmegen. The Netherlands. /Radboud University Medical Center. Department of Internal Medicine and Radboud Center for Infectious Diseases. Nijmegen. The Netherland.s.Radboud University Medical Center. Radboud Institute of Molecular Life Sciences. Department of Human Genetics. Nijmegen. The Netherlands.Schinzel-Giedion syndrome (SGS) is a rare developmental disorder characterized by multiple malformations, severe neurological alterations and increased risk of malignancy. SGS is caused by de novo germline mutations clustering to a 12bp hotspot in exon 4 of SETBP1. Mutations in this hotspot disrupt a degron, a signal for the regulation of protein degradation, and lead to the accumulation of SETBP1 protein. Overlapping SETBP1 hotspot mutations have been observed recurrently as somatic events in leukemia. We collected clinical information of 47 SGS patients (including 26 novel cases) with germline SETBP1 mutations and of four individuals with a milder phenotype caused by de novo germline mutations adjacent to the SETBP1 hotspot. Different mutations within and around the SETBP1 hotspot have varying effects on SETBP1 stability and protein levels in vitro and in in silico modeling. Substitutions in SETBP1 residue I871 result in a weak increase in protein levels and mutations affecting this residue are significantly more frequent in SGS than in leukemia. On the other hand, substitutions in residue D868 lead to the largest increase in protein levels. Individuals with germline mutations affecting D868 have enhanced cell proliferation in vitro and higher incidence of cancer compared to patients with other germline SETBP1 mutations. Our findings substantiate that, despite their overlap, somatic SETBP1 mutations driving malignancy are more disruptive to the degron than germline SETBP1 mutations causing SGS. Additionally, this suggests that the functional threshold for the development of cancer driven by the disruption of the SETBP1 degron is higher than for the alteration in prenatal development in SGS. Drawing on previous studies of somatic SETBP1 mutations in leukemia, our results reveal a genotype-phenotype correlation in germline SETBP1 mutations spanning a molecular, cellular and clinical phenotype.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/45518/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALpgen.1006683(3).pdfpgen.1006683(3).pdfapplication/pdf2369443https://www.arca.fiocruz.br/bitstream/icict/45518/2/pgen.1006683%283%29.pdf453f687f6dc08e19ec19de5900a5782dMD52TEXTpgen.1006683(3).pdf.txtpgen.1006683(3).pdf.txtExtracted texttext/plain89627https://www.arca.fiocruz.br/bitstream/icict/45518/3/pgen.1006683%283%29.pdf.txtd06039140d40e344681a002e45046f67MD53icict/455182021-01-07 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dc.title.pt_BR.fl_str_mv Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies
title Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies
spellingShingle Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies
Acuna-Hidalgo, Rocio
Abnormalities, Multiple / genetics
Abnormalities, Multiple / metabolism
Abnormalities, Multiple / pathology
Blotting, Western
Carrier Proteins / genetics
Carrier Proteins / metabolism
Cell Line
Cell Proliferation / genetics
Cell Transformation, Neoplastic / genetics
Child
Child, Preschool
Craniofacial Abnormalities / genetics
Craniofacial Abnormalities / metabolism
Craniofacial Abnormalities / pathology
Female
Gene Expression Profiling
Genetic Association Studies
Genetic Predisposition to Disease / genetics
Germ-Line Mutation
HEK293 Cells
Hand Deformities, Congenital / genetics
Hand Deformities, Congenital / metabolism
Hand Deformities, Congenital / pathology
Hematologic Neoplasms / genetics
Phenotype
Nuclear Proteins / metabolism
Hematologic Neoplasms / metabolism
Hematologic Neoplasms / pathology
Nuclear Proteins / genetics
Nails, Malformed / pathology
Nails, Malformed / metabolism
Nails, Malformed / genetics
Mutation
Male
Humans
Infant
Intellectual Disability / pathology
Intellectual Disability / genetics
Infant, Newborn
title_short Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies
title_full Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies
title_fullStr Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies
title_full_unstemmed Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies
title_sort Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies
author Acuna-Hidalgo, Rocio
author_facet Acuna-Hidalgo, Rocio
Deriziotis, Pelagia
Steehouwer, Marloes
Gilissen, Christian
Graham, Sarah A.
van Dam, Sipko
Hoover-Fong, Julie
Telegrafi, Aida B.
Destree, Anne
Smigiel, Robert
Lambie, Lindsday A.
Kayserili, Hülya
Altunoglu, Umut
Lapi, Elisabetta
Uzielli, Maria Luisa
Aracena, Mariana
Nur, Banu G.
Mihci, Ercan
Moreira, Lilia M. A.
Borges Ferreira, Viviane
Horovitz, Dafne Dain Gandelman
Rocha, Katia M. da
Jezela-Stanek, Aleksandra
Brooks, Alice S.
Reutter, Heiko
Cohen, Julie S.
Fatemi, Ali
Smitka, Martin
Grebe, Theresa A.
Di Donato, Nataliya
Deshpande, Charu
Vandersteen, Anthony
Marques Lourenço, Charles
Dufke, Andreas
Rossier, Eva
Andre, Gwenaelle
Baumer, Alessandra
Spencer, Careni
McGaughran, Julie
Franke, Lude
Veltman, Joris A.
De Vries, Bert B. A.
Schinzel, Albert
Fisher, Simon E.
Hoischen, Alexander
van Bon, Bregje W.
author_role author
author2 Deriziotis, Pelagia
Steehouwer, Marloes
Gilissen, Christian
Graham, Sarah A.
van Dam, Sipko
Hoover-Fong, Julie
Telegrafi, Aida B.
Destree, Anne
Smigiel, Robert
Lambie, Lindsday A.
Kayserili, Hülya
Altunoglu, Umut
Lapi, Elisabetta
Uzielli, Maria Luisa
Aracena, Mariana
Nur, Banu G.
Mihci, Ercan
Moreira, Lilia M. A.
Borges Ferreira, Viviane
Horovitz, Dafne Dain Gandelman
Rocha, Katia M. da
Jezela-Stanek, Aleksandra
Brooks, Alice S.
Reutter, Heiko
Cohen, Julie S.
Fatemi, Ali
Smitka, Martin
Grebe, Theresa A.
Di Donato, Nataliya
Deshpande, Charu
Vandersteen, Anthony
Marques Lourenço, Charles
Dufke, Andreas
Rossier, Eva
Andre, Gwenaelle
Baumer, Alessandra
Spencer, Careni
McGaughran, Julie
Franke, Lude
Veltman, Joris A.
De Vries, Bert B. A.
Schinzel, Albert
Fisher, Simon E.
Hoischen, Alexander
van Bon, Bregje W.
author2_role author
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author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
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author
author
author
author
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author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Acuna-Hidalgo, Rocio
Deriziotis, Pelagia
Steehouwer, Marloes
Gilissen, Christian
Graham, Sarah A.
van Dam, Sipko
Hoover-Fong, Julie
Telegrafi, Aida B.
Destree, Anne
Smigiel, Robert
Lambie, Lindsday A.
Kayserili, Hülya
Altunoglu, Umut
Lapi, Elisabetta
Uzielli, Maria Luisa
Aracena, Mariana
Nur, Banu G.
Mihci, Ercan
Moreira, Lilia M. A.
Borges Ferreira, Viviane
Horovitz, Dafne Dain Gandelman
Rocha, Katia M. da
Jezela-Stanek, Aleksandra
Brooks, Alice S.
Reutter, Heiko
Cohen, Julie S.
Fatemi, Ali
Smitka, Martin
Grebe, Theresa A.
Di Donato, Nataliya
Deshpande, Charu
Vandersteen, Anthony
Marques Lourenço, Charles
Dufke, Andreas
Rossier, Eva
Andre, Gwenaelle
Baumer, Alessandra
Spencer, Careni
McGaughran, Julie
Franke, Lude
Veltman, Joris A.
De Vries, Bert B. A.
Schinzel, Albert
Fisher, Simon E.
Hoischen, Alexander
van Bon, Bregje W.
dc.subject.mesh.pt_BR.fl_str_mv Abnormalities, Multiple / genetics
Abnormalities, Multiple / metabolism
Abnormalities, Multiple / pathology
Blotting, Western
Carrier Proteins / genetics
Carrier Proteins / metabolism
Cell Line
Cell Proliferation / genetics
Cell Transformation, Neoplastic / genetics
Child
Child, Preschool
Craniofacial Abnormalities / genetics
Craniofacial Abnormalities / metabolism
Craniofacial Abnormalities / pathology
Female
Gene Expression Profiling
Genetic Association Studies
Genetic Predisposition to Disease / genetics
Germ-Line Mutation
HEK293 Cells
Hand Deformities, Congenital / genetics
Hand Deformities, Congenital / metabolism
Hand Deformities, Congenital / pathology
Hematologic Neoplasms / genetics
Phenotype
Nuclear Proteins / metabolism
Hematologic Neoplasms / metabolism
Hematologic Neoplasms / pathology
Nuclear Proteins / genetics
Nails, Malformed / pathology
Nails, Malformed / metabolism
Nails, Malformed / genetics
Mutation
Male
Humans
Infant
Intellectual Disability / pathology
Intellectual Disability / genetics
Infant, Newborn
topic Abnormalities, Multiple / genetics
Abnormalities, Multiple / metabolism
Abnormalities, Multiple / pathology
Blotting, Western
Carrier Proteins / genetics
Carrier Proteins / metabolism
Cell Line
Cell Proliferation / genetics
Cell Transformation, Neoplastic / genetics
Child
Child, Preschool
Craniofacial Abnormalities / genetics
Craniofacial Abnormalities / metabolism
Craniofacial Abnormalities / pathology
Female
Gene Expression Profiling
Genetic Association Studies
Genetic Predisposition to Disease / genetics
Germ-Line Mutation
HEK293 Cells
Hand Deformities, Congenital / genetics
Hand Deformities, Congenital / metabolism
Hand Deformities, Congenital / pathology
Hematologic Neoplasms / genetics
Phenotype
Nuclear Proteins / metabolism
Hematologic Neoplasms / metabolism
Hematologic Neoplasms / pathology
Nuclear Proteins / genetics
Nails, Malformed / pathology
Nails, Malformed / metabolism
Nails, Malformed / genetics
Mutation
Male
Humans
Infant
Intellectual Disability / pathology
Intellectual Disability / genetics
Infant, Newborn
description Radboud University Medical Center. Radboud Institute of Molecular Life Sciences. Department of Human Genetics. Nijmegen. The Netherlands.
publishDate 2017
dc.date.issued.fl_str_mv 2017
dc.date.accessioned.fl_str_mv 2021-01-06T19:42:43Z
dc.date.available.fl_str_mv 2021-01-06T19:42:43Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv Acuna-Hidalgo R, Deriziotis P, Steehouwer M, Gilissen C, Graham SA, van Dam S, Hoover-Fong J, Telegrafi AB, Destree A, Smigiel R, Lambie LA, Kayserili H, Altunoglu U, Lapi E, Uzielli ML, Aracena M, Nur BG, Mihci E, Moreira LM, Borges Ferreira V, Horovitz DD, da Rocha KM, Jezela-Stanek A, Brooks AS, Reutter H, Cohen JS, Fatemi A, Smitka M, Grebe TA, Di Donato N, Deshpande C, Vandersteen A, Marques Lourenço C, Dufke A, Rossier E, Andre G, Baumer A, Spencer C, McGaughran J, Franke L, Veltman JA, De Vries BB, Schinzel A, Fisher SE, Hoischen A, van Bon BW. Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies. PLoS Genet. 2017 Mar 27;13(3):e1006683. doi: 10.1371/journal.pgen.1006683. PMID: 28346496; PMCID: PMC5386295.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/45518
dc.identifier.issn.pt_BR.fl_str_mv 1553-7390
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pgen.1006683
identifier_str_mv Acuna-Hidalgo R, Deriziotis P, Steehouwer M, Gilissen C, Graham SA, van Dam S, Hoover-Fong J, Telegrafi AB, Destree A, Smigiel R, Lambie LA, Kayserili H, Altunoglu U, Lapi E, Uzielli ML, Aracena M, Nur BG, Mihci E, Moreira LM, Borges Ferreira V, Horovitz DD, da Rocha KM, Jezela-Stanek A, Brooks AS, Reutter H, Cohen JS, Fatemi A, Smitka M, Grebe TA, Di Donato N, Deshpande C, Vandersteen A, Marques Lourenço C, Dufke A, Rossier E, Andre G, Baumer A, Spencer C, McGaughran J, Franke L, Veltman JA, De Vries BB, Schinzel A, Fisher SE, Hoischen A, van Bon BW. Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies. PLoS Genet. 2017 Mar 27;13(3):e1006683. doi: 10.1371/journal.pgen.1006683. PMID: 28346496; PMCID: PMC5386295.
1553-7390
10.1371/journal.pgen.1006683
url https://www.arca.fiocruz.br/handle/icict/45518
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science [Commercial Publisher]
publisher.none.fl_str_mv Public Library of Science [Commercial Publisher]
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/45518/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/45518/2/pgen.1006683%283%29.pdf
https://www.arca.fiocruz.br/bitstream/icict/45518/3/pgen.1006683%283%29.pdf.txt
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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