The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas

Detalhes bibliográficos
Autor(a) principal: Cambruzzi,Eduardo
Data de Publicação: 2017
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Jornal Brasileiro de Patologia e Medicina Laboratorial (Online)
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1676-24442017000500338
Resumo: ABSTRACT Diffuse astrocytoma and glioblastoma (GBM) constitute a group of diffusely infiltrating astrocytic neoplasms, which more commonly arise in cerebral hemispheres of adults. The prevalence of malignant transformation of diffuse astrocytoma to anaplastic astrocytoma and GBM varies from 40% to 75% of cases in different series. Distinct genetic abnormalities are related to neoplastic progression, and the cells prone to glial neoplasm development include progenitor cells, stem cells, or differentiated cells. Primary GBM arises typically de novo, with no previous history of a lower-grade precursor lesion. Secondary GBM evolves from low-grade astrocytoma, is predominant in younger patients, and frequently exhibits isocitrate dehydrogenase (IDH) 1 and 2 mutations. IDH1/2 mutated gliomas have been associated with a better prognosis when compared to IDH-wildtype gliomas. IDH mutations are rare in primary GBM and gliomas arising in children. Evidence suggests that IDH mutations lead to a hypermethylation phenotype and represent early events in tumoral transformation of the central nervous system (CNS) due to the production of the oncometabolite 2-hydroxyglutarate. IDH1 mutations precede tumor protein p53 (TP53) mutations in around 63% of cases of diffuse astrocytomas, and result in loss in 10q and 19q chromosomes. Primary GBMs are also associated with alterations in cell proliferation [epidermal growth fator receptor (EGFR) amplification/mutation, platelet derived growth factor receptor alpha (PDGFRA) amplifications, neurofibromin 1 (NF1) mutations], abnormal apoptotic index [cyclin dependent kinase inhibitor 2A (CDKN2A) homozygous deletion and TP53 mutation], and aberrant progression in G1/S phase of the cell cycle.
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spelling The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomasastrocytomaglioblastomaisocitrate dehydrogenasepathologyprognosisbrainABSTRACT Diffuse astrocytoma and glioblastoma (GBM) constitute a group of diffusely infiltrating astrocytic neoplasms, which more commonly arise in cerebral hemispheres of adults. The prevalence of malignant transformation of diffuse astrocytoma to anaplastic astrocytoma and GBM varies from 40% to 75% of cases in different series. Distinct genetic abnormalities are related to neoplastic progression, and the cells prone to glial neoplasm development include progenitor cells, stem cells, or differentiated cells. Primary GBM arises typically de novo, with no previous history of a lower-grade precursor lesion. Secondary GBM evolves from low-grade astrocytoma, is predominant in younger patients, and frequently exhibits isocitrate dehydrogenase (IDH) 1 and 2 mutations. IDH1/2 mutated gliomas have been associated with a better prognosis when compared to IDH-wildtype gliomas. IDH mutations are rare in primary GBM and gliomas arising in children. Evidence suggests that IDH mutations lead to a hypermethylation phenotype and represent early events in tumoral transformation of the central nervous system (CNS) due to the production of the oncometabolite 2-hydroxyglutarate. IDH1 mutations precede tumor protein p53 (TP53) mutations in around 63% of cases of diffuse astrocytomas, and result in loss in 10q and 19q chromosomes. Primary GBMs are also associated with alterations in cell proliferation [epidermal growth fator receptor (EGFR) amplification/mutation, platelet derived growth factor receptor alpha (PDGFRA) amplifications, neurofibromin 1 (NF1) mutations], abnormal apoptotic index [cyclin dependent kinase inhibitor 2A (CDKN2A) homozygous deletion and TP53 mutation], and aberrant progression in G1/S phase of the cell cycle.Sociedade Brasileira de Patologia Clínica2017-10-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1676-24442017000500338Jornal Brasileiro de Patologia e Medicina Laboratorial v.53 n.5 2017reponame:Jornal Brasileiro de Patologia e Medicina Laboratorial (Online)instname:Sociedade Brasileira de Patologia (SBP)instacron:SBP10.5935/1676-2444.20170055info:eu-repo/semantics/openAccessCambruzzi,Eduardoeng2017-12-14T00:00:00Zoai:scielo:S1676-24442017000500338Revistahttp://www.scielo.br/jbpmlhttps://old.scielo.br/oai/scielo-oai.php||jbpml@sbpc.org.br1678-47741676-2444opendoar:2017-12-14T00:00Jornal Brasileiro de Patologia e Medicina Laboratorial (Online) - Sociedade Brasileira de Patologia (SBP)false
dc.title.none.fl_str_mv The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas
title The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas
spellingShingle The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas
Cambruzzi,Eduardo
astrocytoma
glioblastoma
isocitrate dehydrogenase
pathology
prognosis
brain
title_short The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas
title_full The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas
title_fullStr The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas
title_full_unstemmed The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas
title_sort The role of IDH1/2 mutations in the pathogenesis of secondary glioblastomas
author Cambruzzi,Eduardo
author_facet Cambruzzi,Eduardo
author_role author
dc.contributor.author.fl_str_mv Cambruzzi,Eduardo
dc.subject.por.fl_str_mv astrocytoma
glioblastoma
isocitrate dehydrogenase
pathology
prognosis
brain
topic astrocytoma
glioblastoma
isocitrate dehydrogenase
pathology
prognosis
brain
description ABSTRACT Diffuse astrocytoma and glioblastoma (GBM) constitute a group of diffusely infiltrating astrocytic neoplasms, which more commonly arise in cerebral hemispheres of adults. The prevalence of malignant transformation of diffuse astrocytoma to anaplastic astrocytoma and GBM varies from 40% to 75% of cases in different series. Distinct genetic abnormalities are related to neoplastic progression, and the cells prone to glial neoplasm development include progenitor cells, stem cells, or differentiated cells. Primary GBM arises typically de novo, with no previous history of a lower-grade precursor lesion. Secondary GBM evolves from low-grade astrocytoma, is predominant in younger patients, and frequently exhibits isocitrate dehydrogenase (IDH) 1 and 2 mutations. IDH1/2 mutated gliomas have been associated with a better prognosis when compared to IDH-wildtype gliomas. IDH mutations are rare in primary GBM and gliomas arising in children. Evidence suggests that IDH mutations lead to a hypermethylation phenotype and represent early events in tumoral transformation of the central nervous system (CNS) due to the production of the oncometabolite 2-hydroxyglutarate. IDH1 mutations precede tumor protein p53 (TP53) mutations in around 63% of cases of diffuse astrocytomas, and result in loss in 10q and 19q chromosomes. Primary GBMs are also associated with alterations in cell proliferation [epidermal growth fator receptor (EGFR) amplification/mutation, platelet derived growth factor receptor alpha (PDGFRA) amplifications, neurofibromin 1 (NF1) mutations], abnormal apoptotic index [cyclin dependent kinase inhibitor 2A (CDKN2A) homozygous deletion and TP53 mutation], and aberrant progression in G1/S phase of the cell cycle.
publishDate 2017
dc.date.none.fl_str_mv 2017-10-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.uri.fl_str_mv http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1676-24442017000500338
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1676-24442017000500338
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.5935/1676-2444.20170055
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dc.publisher.none.fl_str_mv
Sociedade Brasileira de Patologia Clínica
publisher.none.fl_str_mv
Sociedade Brasileira de Patologia Clínica
dc.source.none.fl_str_mv Jornal Brasileiro de Patologia e Medicina Laboratorial v.53 n.5 2017
reponame:Jornal Brasileiro de Patologia e Medicina Laboratorial (Online)
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reponame_str Jornal Brasileiro de Patologia e Medicina Laboratorial (Online)
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repository.name.fl_str_mv Jornal Brasileiro de Patologia e Medicina Laboratorial (Online) - Sociedade Brasileira de Patologia (SBP)
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