Low frequency of TERT promoter mutations in gastrointestinal stromal tumors (GISTs)

Somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) gene, mainly at positions c.-124 and c.-146 bp, are frequent in several human cancers; yet its presence in gastrointestinal stromal tumor (GIST) has not been reported to date. Herein, we searched for the presence and clinicopathological association of TERT promoter mutations in genomic DNA from 130 bona fide GISTs. We found TERT promoter mutations in 3.8% (5/130) of GISTs. The c.-124C>T mutation was the most common event, present in 2.3% (3/130), and the c.-146C>T mutation in 1.5% (2/130) of GISTs. No significant association was observed between TERT promoter mutation and patient's clinicopathological features. The present study establishes the low frequency (4%) of TERT promoter mutations in GISTs. Further studies are required to confirm our findings and to elucidate the hypothetical biological and clinical impact of TERT promoter mutation in GIST pathogenesis.

TERT Promoter Mutations Are a Major Indicator of Poor Outcome in Differentiated Thyroid Carcinomas

Context: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers. Objectives: We aimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs). Design: This was a retrospective observational study. Setting and Patients: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years. Main Outcome Measures: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality. Results: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P < .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P = .001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P = .001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01–53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36–415.76; P = .03) in PTCs. Conclusions: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC.

Relatório de estágio em educação pré-escolar e ensino do 1º ciclo do ensino básico

O presente relatório – requisito parcial para obtenção do grau de mestre em Educação Pré-Escolar e Ensino do 1.º Ciclo do Ensino Básico – reflete as experiências e conhecimentos desenvolvidos, resultantes da prática pedagógica supervisionada desenvolvida em dois contextos de estágio: Educação Pré-Escolar e 1.º Ciclo do Ensino Básico. Com efeito, a estudante teve como objetivo descrever, compreender e refletir acerca do processo de prática segundo o desenvolvimento de capacidades e competências substanciais à prática docente. Enquanto (futura) profissional de educação, verifica-se pertinente a mobilização de saberes científicos, pedagógicos e culturais, adquiridos ao longo da formação inicial para que se torne exequível uma prática sustentada. Similarmente, o docente, baseando-se em quadros teóricos e concetuais (amplificados de forma subjetiva e continuada), desenvolverá a sua forma pessoal de pensar e agir nos contextos de práticas reais visando a inclusão e equidade educativas, e a colaboração profissional e reflexiva. Conforme a metodologia de investigação-ação (constituída por várias etapas interligadas – observação, planificação, ação e avaliação, reflexão), a ação da mestranda desenvolveu-se de forma cíclica e articulada, numa perspetiva construtivista – e holística – do conhecimento a erigir pelas crianças (atores centrais do processo) ressalvando-se, igualmente, a pertinência dos demais instrumentos orientadores elaborados no decorrer da ação. Concludentemente, os estágios desenvolvidos nos dois contextos facultaram a edificação de uma postura profissional, reflexiva e investigativa, promotora da tomada de decisões em contexto de prática reafirmando-se competências profissionais e pessoais e valorando-se, efetivamente, a formação ao longo da vida para aquele que se constitui um docente generalista.