Loss of 5 '-Methylthioadenosine Phosphorylase (MTAP) is Frequent in High-Grade Gliomas; Nevertheless, it is Not Associated with Higher Tumor Aggressiveness

Registro completo de metadados
Autor(es): dc.contributorBarretos Canc Hosp-
Autor(es): dc.contributorAC Camargo Canc Ctr-
Autor(es): dc.contributorInst Canc Res-
Autor(es): dc.contributorBarretos Sch Hlth Sci-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorUniv Minho-
Autor(es): dc.contributor3Bs PT Govt Associate Lab-
Autor(es): dc.creatorMenezes, Weder Pereira de-
Autor(es): dc.creatorOliveira Silva, Viviane Aline-
Autor(es): dc.creatorFaria Gomes, Izabela Natalia-
Autor(es): dc.creatorRosa, Marcela Nunes-
Autor(es): dc.creatorCorcoll Spina, Maria Luisa-
Autor(es): dc.creatorCarloni, Adriana Cruvinel-
Autor(es): dc.creatorVieira Alves, Ana Laura-
Autor(es): dc.creatorMelendez, Matias-
Autor(es): dc.creatorAlmeida, Gisele Caravina-
Autor(es): dc.creatorSilva, Luciane Sussuchi da-
Autor(es): dc.creatorClara, Carlos-
Autor(es): dc.creatorCunha, Isabela Werneck da-
Autor(es): dc.creatorMaroso Hajj, Glaucia Noeli-
Autor(es): dc.creatorJones, Chris-
Autor(es): dc.creatorBidinotto, Lucas Tadeu [UNESP]-
Autor(es): dc.creatorReis, Rui Manuel-
Data de aceite: dc.date.accessioned2022-02-22T00:10:16Z-
Data de disponibilização: dc.date.available2022-02-22T00:10:16Z-
Data de envio: dc.date.issued2020-12-09-
Data de envio: dc.date.issued2020-12-09-
Data de envio: dc.date.issued2020-01-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/cells9020492-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/196723-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/196723-
Descrição: dc.descriptionThe 5'-methylthioadenosine phosphorylase (MTAP) gene is located in the chromosomal region 9p21. MTAP deletion is a frequent event in a wide variety of human cancers; however, its biological role in tumorigenesis remains unclear. The purpose of this study was to characterize the MTAP expression profile in a series of gliomas and to associate it with patients' clinicopathological features. Moreover, we sought to evaluate, through glioma gene-edited cell lines, the biological impact of MTAP in gliomas. MTAP expression was evaluated in 507 glioma patients by immunohistochemistry (IHC), and the expression levels were associated with patients' clinicopathological features. Furthermore, an in silico study was undertaken using genomic databases totalizing 350 samples. In glioma cell lines, MTAP was edited, and following MTAP overexpression and knockout (KO), a transcriptome analysis was performed by NanoString Pan-Cancer Pathways panel. Moreover, MTAP's role in glioma cell proliferation, migration, and invasion was evaluated. Homozygous deletion of 9p21 locus was associated with a reduction of MTAP mRNA expression in the TCGA (The Cancer Genome Atlas) - glioblastoma dataset (p < 0.01). In addition, the loss of MTAP expression was markedly high in high-grade gliomas (46.6% of cases) determined by IHC and Western blotting (40% of evaluated cell lines). Reduced MTAP expression was associated with a better prognostic in the adult glioblastoma dataset (p < 0.001). Nine genes associated with five pathways were differentially expressed in MTAP-knockout (KO) cells, with six upregulated and three downregulated in MTAP. Analysis of cell proliferation, migration, and invasion did not show any significant differences between MTAP gene-edited and control cells. Our results integrating data from patients as well as in silico and in vitro models provide evidence towards the lack of strong biological importance of MTAP in gliomas. Despite the frequent loss of MTAP, it seems not to have a clinical impact in survival and does not act as a canonic tumor suppressor gene in gliomas.-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionBarretos Cancer Hospital-
Descrição: dc.descriptionPublic Ministry of Labor Campinas (Research, Prevention and Education of Occupational Cancer)-
Descrição: dc.descriptionNational Institute for Health Research (NIHR) Biomedical Research Center at the Royal Marsden-
Descrição: dc.descriptionInstitute of Cancer Research in London-
Descrição: dc.descriptionNIHR-
Descrição: dc.descriptionBarretos Canc Hosp, Mol Oncol Res Ctr, BR-14784400 Barretos, SP, Brazil-
Descrição: dc.descriptionBarretos Canc Hosp, Dept Pathol, BR-14784400 Barretos, SP, Brazil-
Descrição: dc.descriptionBarretos Canc Hosp, Dept Neurosurg, BR-14784400 Barretos, SP, Brazil-
Descrição: dc.descriptionAC Camargo Canc Ctr, BR-01508010 Sao Paulo, SP, Brazil-
Descrição: dc.descriptionInst Canc Res, London SW7 3RP, England-
Descrição: dc.descriptionBarretos Sch Hlth Sci, Dr Paulo Prata FACISB, BR-14785002 Barretos, SP, Brazil-
Descrição: dc.descriptionUniv Estadual Paulista Unesp, Botucatu Med Sch, Dept Pathol, BR-18618970 Botucatu, SP, Brazil-
Descrição: dc.descriptionUniv Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, P-4710057 Braga, Portugal-
Descrição: dc.description3Bs PT Govt Associate Lab, P-4806909 Braga, Portugal-
Descrição: dc.descriptionUniv Estadual Paulista Unesp, Botucatu Med Sch, Dept Pathol, BR-18618970 Botucatu, SP, Brazil-
Descrição: dc.descriptionFAPESP: 2016/06833-2-
Descrição: dc.descriptionFAPESP: 2016/18907-0-
Descrição: dc.descriptionFAPESP: 2017/22305-9-
Descrição: dc.descriptionCNPq: 100707/2014-9-
Descrição: dc.descriptionCNPq: 116477/2014-8-
Descrição: dc.descriptionCNPq: 1282245/2014-0-
Descrição: dc.descriptionCNPq: 472447/2013-0-
Formato: dc.format24-
Idioma: dc.languageen-
Publicador: dc.publisherMdpi-
Relação: dc.relationCells-
???dc.source???: dc.sourceWeb of Science-
Palavras-chave: dc.subjectglioma-
Palavras-chave: dc.subjectglioblastoma-
Palavras-chave: dc.subject5'-methylthioadenosine phosphorylase (MTAP)-
Palavras-chave: dc.subjectimmunohistochemistry-
Palavras-chave: dc.subjecttumor biology-
Palavras-chave: dc.subjectproliferation-
Palavras-chave: dc.subjectmigration-
Palavras-chave: dc.subjectinvasion-
Título: dc.titleLoss of 5 '-Methylthioadenosine Phosphorylase (MTAP) is Frequent in High-Grade Gliomas; Nevertheless, it is Not Associated with Higher Tumor Aggressiveness-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

Não existem arquivos associados a este item.