DGCR8 microprocessor defect and deregulation of its expression in thyroid lesions

• Autor(a) principal: Rodrigues, Lia Cristiana Gomes
• Data de Publicação: 2021
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.22/19706
• topic: mIRNA; Microprocessor complex; Thyroid cancer; DGCR8; p.(E518K)

Deregulation of microRNA (miRNA) processing is a driver event in several tumors including thyroid cancer. DiGeorge Critical Region 8 (DGCR8) gene holds a critical role in miRNA biogenesis, as a microprocessor complex componente, and in the development of the thyroid. Previous studies identified DGCR8mutation – the variant c.1552G˃Ap.(E518K) – in cases of thyroid cancer and proposed to cause a familial syndrome characterized by multinodular goitre (MNG) and schwannomatosis. The goal of this study was to characterize the variant p.(E518K) of DGCR8 in thyroid lesions and evaluate its expression. A series of thyroid lesions were evaluated by sequencing fot the c.1552G˃Ap.(E518K) variant. When frozen tissue was available, DGCR8 mRNA expression was analysed by qPCR. Formalin-fixed parafin-embedded tissues were studied for DGCR8 immunoexpression. In this work, i tis decribed for the first time the hotspot p.(E518K) mutation in a case poorly differentiated thyroid carcinoma. This case displayed DGCR8 mRNA expression comparable to the basal level whereas the protein expression was highly aberrant. Deregulation of folicular.patterned tumours was also observed at the DGCR8 mRNA level. The obtained data suggest that DGCR8 could have a role in thyroid tumorigenesis, particularlyin folicular-patterned thyroid tumours.