Study of hTERT and Histone 3 Mutations in Medulloblastoma

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dc.citation.issue2
dc.citation.volume84
dc.contributor.authorViana-Pereira, Marta
dc.contributor.authorAlmeida, Gisele Caravina
dc.contributor.authorStávale, João Norberto [UNIFESP]
dc.contributor.authorMalheiro, Susana [UNIFESP]
dc.contributor.authorClara, Carlos
dc.contributor.authorLobo, Patricia
dc.contributor.authorPimentel, Jose
dc.contributor.authorReis, Rui Manuel
dc.coverageBasel
dc.date.accessioned2020-07-31T12:46:50Z
dc.date.available2020-07-31T12:46:50Z
dc.date.issued2017
dc.description.abstractHotspot activating mutations of the telomerase reverse transcriptase (hTERT) promoter region were recently described in several tumor types. These mutations lead to enhanced expression of telomerase, being responsible for telomere maintenance and allowing continuous cell division. Additionally, there are alternative telomere maintenance mechanisms, associated with histone H3 mutations, responsible for disrupting the histone code and affecting the regulation of transcription. Here, we investigated the clinical relevance of these mechanistically related molecules in nnedulloblastoma. Sixty-nine medulloblastomas, formalin fixed and paraffin embedded, from a cohort of patients aged 1.5-70 years, were used to investigate the hotspot mutations of the hTERT promoter region, i.e. H3F3A and HIST1H3B, using Sanger sequencing. We successfully sequenced hTERT in all 69 medulloblastoma samples and identified a total of 19 mutated cases (27.5%). c.-124:G>A and c.-146:G>A mutations were detected, respectively, in 16 and 3 samples. Similar to previous reports, hTERT mutations were more frequent in older patients (p < 0.0001), being found only in 5 patients <20 years of age. In addition, hTERT-mutated tumors were more frequently recurrent (p = 0.026) and hTERT mutations were significantly enriched in tumors located in the right cerebellar hemisphere (p = 0.039). No mutations were found on the H3F3A or HIST1H3B genes. hTERT promoter mutations are frequent in medulloblastoma and are associated with older patients, prone to recurrence and located in the right cerebellar hemisphere. On the other hand, histone 3 mutations do not seem to be present in nnedulloblastoma. (C) 2016 S. Karger AG, Baselen
dc.description.affiliationUniv Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Campus Gualtar, P-4710057 Braga, Portugal
dc.description.affiliationICVS 3Bs PT Govt Associate Lab, Braga, Portugal
dc.description.affiliationHosp Santa Maria, Lisbon Fac Med, Inst Mol Med, Neuropathol Lab, Lisbon, Portugal
dc.description.affiliationBarretos Canc Hosp, Dept Pathol, Barretos, Brazil
dc.description.affiliationBarretos Canc Hosp, Dept Neurosurg, Barretos, Brazil
dc.description.affiliationBarretos Canc Hosp, Mol Oncol Res Ctr, Barretos, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Pathol, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Neurol & Neurosurg, Sao Paulo, Brazil
dc.description.affiliationUnifespDepartment of Pathology, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
dc.description.affiliationUnifespDepartment of Neurology and Neurosurgery, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipCNPq/Universal [475358/2011-2]
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2012/19590-0]
dc.description.sponsorshipFundacao para a Ciencia e Tecnologia (FCT) [PTDC/SAU-ONC/115513/2009]
dc.description.sponsorshipPrograma Operacional Regional do Norte (ON.2-O Novo Norte), Quadro de Referencia Estrategico Nacional (QREN)
dc.description.sponsorshipFundo Europeu de Desenvolvimento Regional (FEDER)
dc.description.sponsorshipFCT [SFRH/BPD/104290/2014]
dc.description.sponsorshipIDCNPq/Universal [475358/2011-2]
dc.description.sponsorshipIDFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2012/19590-0]
dc.description.sponsorshipIDFundacao para a Ciencia e Tecnologia (FCT) [PTDC/SAU-ONC/115513/2009]
dc.description.sponsorshipIDPrograma Operacional Regional do Norte (ON.2-O Novo Norte), Quadro de Referencia Estrategico Nacional (QREN)
dc.description.sponsorshipIDFundo Europeu de Desenvolvimento Regional (FEDER)
dc.description.sponsorshipIDFCT [SFRH/BPD/104290/2014]
dc.format.extent108-113
dc.identifierhttp://dx.doi.org/10.1159/000448922
dc.identifier.citationPathobiology. Basel, v. 84, n. 2, p. 108-113, 2017.
dc.identifier.doi10.1159/000448922
dc.identifier.issn1015-2008
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56401
dc.identifier.wosWOS:000394725600006
dc.language.isoeng
dc.publisherKarger
dc.relation.ispartofPathobiology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjecthTERTen
dc.subjectMutationsen
dc.subjectMedulloblastomaen
dc.subjectBiomarkersen
dc.titleStudy of hTERT and Histone 3 Mutations in Medulloblastomaen
dc.typeinfo:eu-repo/semantics/article
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