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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Study of hTERT and Histone 3 Mutations in Medulloblastoma

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Author(s):
Viana-Pereira, Marta ; Almeida, Gisele Caravina ; Stavale, Joao Norberto ; Malheiro, Susana ; Clara, Carlos ; Lobo, Patricia ; Pimentel, Jose ; Reis, Rui Manuel
Total Authors: 8
Document type: Journal article
Source: PATHOBIOLOGY; v. 84, n. 2, p. 108-113, 2017.
Web of Science Citations: 3
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 (AU)

FAPESP's process: 12/19590-0 - Mutational profile of glioblastoma primary cultures
Grantee:Rui Manuel Vieira Reis
Support Opportunities: Regular Research Grants