Study of hTERT and Histone 3 Mutations in Medulloblastoma

CNPq/Universal (475358/2011-2), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; 2012/19590-0) and Fundação para a Ciência e Tecnologia (FCT; PTDC/SAU-ONC/115513/2009) grants to R.M.R. The project was cofinanced by Programa Operacional Regional do Norte (ON.2-O Novo Norte), Quadro de Referência Estratégico Nacional (QREN) and Fundo Europeu de Desenvol- vimento Regional (FEDER). M.V.-P. is the recipient of an FCT Post-Doctorate Research Fellowship (SFRH/BPD/104290/2014)
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
This study was partially supported by CNPq/Universal (475358/2011-2), Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP; 2012/19590-0) and Fundacao para a Ciencia e Tecnologia (FCT; PTDC/SAU-ONC/115513/2009) grants to R.M.R. The project was cofinanced by Programa Operacional Regional do Norte (ON.2-O Novo Norte), Quadro de Referencia Estrategico Nacional (QREN) and Fundo Europeu de Desenvolvimento Regional (FEDER). M.V.-P. is the recipient of an FCT Post-Doctorate Research Fellowship (SFRH/BPD/104290/2014).
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