Study of hTERT and Histone 3 Mutations in Medulloblastoma

Study of hTERT and Histone 3 Mutations in Medulloblastoma

Author Viana-Pereira, Marta Google Scholar
Almeida, Gisele Caravina Google Scholar
Stávale, João Norberto Autor UNIFESP Google Scholar
Malheiro, Susana Autor UNIFESP Google Scholar
Clara, Carlos Google Scholar
Lobo, Patricia Google Scholar
Pimentel, Jose Google Scholar
Reis, Rui Manuel Google Scholar
Abstract Hotspot 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, Basel
Keywords hTERT
Mutations
Medulloblastoma
Biomarkers
xmlui.dri2xhtml.METS-1.0.item-coverage Basel
Language English
Sponsor CNPq/Universal [475358/2011-2]
Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2012/19590-0]
Fundacao para a Ciencia e Tecnologia (FCT) [PTDC/SAU-ONC/115513/2009]
Programa Operacional Regional do Norte (ON.2-O Novo Norte), Quadro de Referencia Estrategico Nacional (QREN)
Fundo Europeu de Desenvolvimento Regional (FEDER)
FCT [SFRH/BPD/104290/2014]
Grant number CNPq/Universal [475358/2011-2]
Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2012/19590-0]
Fundacao para a Ciencia e Tecnologia (FCT) [PTDC/SAU-ONC/115513/2009]
Programa Operacional Regional do Norte (ON.2-O Novo Norte), Quadro de Referencia Estrategico Nacional (QREN)
Fundo Europeu de Desenvolvimento Regional (FEDER)
FCT [SFRH/BPD/104290/2014]
Date 2017
Published in Pathobiology. Basel, v. 84, n. 2, p. 108-113, 2017.
ISSN 1015-2008 (Sherpa/Romeo, impact factor)
Publisher Karger
Extent 108-113
Origin http://dx.doi.org/10.1159/000448922
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000394725600006
URI https://repositorio.unifesp.br/handle/11600/56401

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