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Mutation analysis of B-RAF gene in human gliomas

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Resumo:The RAS/RAF/MEK/ERK kinase pathway is pivotal in the transduction of mitogenic stimuli from activated growth factor receptors, which regulates cell proliferation, survival, and differentiation. Up-regulation of this pathway due to RAS mutations is found in approximately 30% of human tumors. Recently, activating mutations of B-RAF were identified in a large proportion of human cancers. Gliomas are the most frequent primary central nervous system tumors and the molecular mechanisms that underlie the development and progression of these tumors are far from being completely understood. The purpose of this study was to clarify the incidence of B-RAF mutations and their possible relation with tumor progression in a series of 82 human gliomas, including 49 astrocytic and 33 oligodendroglial tumors. The analysis of B-RAF hotspot regions, exons 11 and 15, showed presence of B-RAF mutations in only 2 out of 34 (6%) glioblastomas, and absence in the remaining histological types. Both mutations were located in the hotspot residue 600 (V600E) at exon 15, which leads to constitutive B-RAF kinase activity. These data suggest that activating mutations of B-RAF are not a frequent event in gliomas; nevertheless, when present they are associated with highgrade malignant lesions.
Autores principais:Basto, Diana
Outros Autores:Trovisco, Vítor; Lopes, José M.; Martins, Albino; Pardal, Fernando; Soares, Paula; Reis, R. M.
Assunto:Gliomas Glioblastoma Oligodendrogliomas B-RAF RAS signaling
Ano:2005
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho
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author Basto, Diana
author2 Trovisco, Vítor
Lopes, José M.
Martins, Albino
Pardal, Fernando
Soares, Paula
Reis, R. M.
author2_role author
author
author
author
author
author
author_facet Basto, Diana
Trovisco, Vítor
Lopes, José M.
Martins, Albino
Pardal, Fernando
Soares, Paula
Reis, R. M.
author_role author
contributor_name_str_mv Universidade do Minho
country_str PT
creators_json_txt [{\"Person.name\":\"Basto, Diana\"},{\"Person.name\":\"Trovisco, Vítor\"},{\"Person.name\":\"Lopes, José M.\"},{\"Person.name\":\"Martins, Albino\"},{\"Person.name\":\"Pardal, Fernando\"},{\"Person.name\":\"Soares, Paula\"},{\"Person.name\":\"Reis, R. M.\"}]
datacite.contributors.contributor.contributorName.fl_str_mv Universidade do Minho
datacite.creators.creator.creatorName.fl_str_mv Basto, Diana
Trovisco, Vítor
Lopes, José M.
Martins, Albino
Pardal, Fernando
Soares, Paula
Reis, R. M.
datacite.date.Accepted.fl_str_mv 2005-05-01T00:00:00Z
datacite.date.available.fl_str_mv 2006-10-19T15:21:08Z
datacite.date.embargoed.fl_str_mv 2006-10-19T15:21:08Z
datacite.rights.fl_str_mv http://purl.org/coar/access_right/c_abf2
datacite.subjects.subject.fl_str_mv Gliomas
Glioblastoma
Oligodendrogliomas
B-RAF
RAS signaling
datacite.titles.title.fl_str_mv Mutation analysis of B-RAF gene in human gliomas
dc.contributor.none.fl_str_mv Universidade do Minho
dc.creator.none.fl_str_mv Basto, Diana
Trovisco, Vítor
Lopes, José M.
Martins, Albino
Pardal, Fernando
Soares, Paula
Reis, R. M.
dc.date.Accepted.fl_str_mv 2005-05-01T00:00:00Z
dc.date.available.fl_str_mv 2006-10-19T15:21:08Z
dc.date.embargoed.fl_str_mv 2006-10-19T15:21:08Z
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv https://hdl.handle.net/1822/5682
dc.language.none.fl_str_mv eng
dc.publisher.none.fl_str_mv Springer
dc.rights.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.subject.none.fl_str_mv Gliomas
Glioblastoma
Oligodendrogliomas
B-RAF
RAS signaling
dc.title.fl_str_mv Mutation analysis of B-RAF gene in human gliomas
dc.type.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
description The RAS/RAF/MEK/ERK kinase pathway is pivotal in the transduction of mitogenic stimuli from activated growth factor receptors, which regulates cell proliferation, survival, and differentiation. Up-regulation of this pathway due to RAS mutations is found in approximately 30% of human tumors. Recently, activating mutations of B-RAF were identified in a large proportion of human cancers. Gliomas are the most frequent primary central nervous system tumors and the molecular mechanisms that underlie the development and progression of these tumors are far from being completely understood. The purpose of this study was to clarify the incidence of B-RAF mutations and their possible relation with tumor progression in a series of 82 human gliomas, including 49 astrocytic and 33 oligodendroglial tumors. The analysis of B-RAF hotspot regions, exons 11 and 15, showed presence of B-RAF mutations in only 2 out of 34 (6%) glioblastomas, and absence in the remaining histological types. Both mutations were located in the hotspot residue 600 (V600E) at exon 15, which leads to constitutive B-RAF kinase activity. These data suggest that activating mutations of B-RAF are not a frequent event in gliomas; nevertheless, when present they are associated with highgrade malignant lesions.
dirty 0
eu_rights_str_mv openAccess
format article
fulltext.url.fl_str_mv https://prod-dspace.uminho.pt/bitstreams/ad1fb425-9a8f-4014-b5be-0564c5e4d730/download
id rum_a34b6f608ea059dad54ffefc9c8a1b5c
identifier.url.fl_str_mv https://hdl.handle.net/1822/5682
instacron_str repositorium
institution Universidade do Minho
instname_str Universidade do Minho
language eng
network_acronym_str rum
network_name_str RepositóriUM - Universidade do Minho
oai_identifier_str oai:repositorium.uminho.pt:1822/5682
organization_str_mv urn:organizationAcronym:repositorium
person_str_mv Basto, Diana
Trovisco, Vítor
Lopes, José M.
Martins, Albino
Pardal, Fernando
Soares, Paula
Reis, R. M.
publishDate 2005
publisher.none.fl_str_mv Springer
reponame_str RepositóriUM - Universidade do Minho
repository_id_str urn:repositoryAcronym:rum
service_str_mv urn:repositoryAcronym:rum
spelling engSpringerengThe RAS/RAF/MEK/ERK kinase pathway is pivotal in the transduction of mitogenic stimuli from activated growth factor receptors, which regulates cell proliferation, survival, and differentiation. Up-regulation of this pathway due to RAS mutations is found in approximately 30% of human tumors. Recently, activating mutations of B-RAF were identified in a large proportion of human cancers. Gliomas are the most frequent primary central nervous system tumors and the molecular mechanisms that underlie the development and progression of these tumors are far from being completely understood. The purpose of this study was to clarify the incidence of B-RAF mutations and their possible relation with tumor progression in a series of 82 human gliomas, including 49 astrocytic and 33 oligodendroglial tumors. The analysis of B-RAF hotspot regions, exons 11 and 15, showed presence of B-RAF mutations in only 2 out of 34 (6%) glioblastomas, and absence in the remaining histological types. Both mutations were located in the hotspot residue 600 (V600E) at exon 15, which leads to constitutive B-RAF kinase activity. These data suggest that activating mutations of B-RAF are not a frequent event in gliomas; nevertheless, when present they are associated with highgrade malignant lesions.application/pdfengMutation analysis of B-RAF gene in human gliomasBasto, DianaTrovisco, VítorLopes, José M.Martins, AlbinoPardal, FernandoSoares, PaulaReis, R. M.HostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptISSNIsPartOf0001-6322DOIIsPartOf10.1007/s00401-004-0936-x2006-10-19T15:21:08Z2005-052005-05-01T00:00:00ZHandlehttps://hdl.handle.net/1822/5682http://purl.org/coar/access_right/c_abf2open accessGliomasGlioblastomaOligodendrogliomasB-RAFRAS signaling243595 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://prod-dspace.uminho.pt/bitstreams/ad1fb425-9a8f-4014-b5be-0564c5e4d730/download
spellingShingle Mutation analysis of B-RAF gene in human gliomas
Basto, Diana
Gliomas
Glioblastoma
Oligodendrogliomas
B-RAF
RAS signaling
status SINGLETON
subject.fl_str_mv Gliomas
Glioblastoma
Oligodendrogliomas
B-RAF
RAS signaling
title Mutation analysis of B-RAF gene in human gliomas
title_full Mutation analysis of B-RAF gene in human gliomas
title_fullStr Mutation analysis of B-RAF gene in human gliomas
title_full_unstemmed Mutation analysis of B-RAF gene in human gliomas
title_short Mutation analysis of B-RAF gene in human gliomas
title_sort Mutation analysis of B-RAF gene in human gliomas
topic Gliomas
Glioblastoma
Oligodendrogliomas
B-RAF
RAS signaling
topic_facet Gliomas
Glioblastoma
Oligodendrogliomas
B-RAF
RAS signaling
url https://hdl.handle.net/1822/5682
visible 1