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Frequency of TERT promoter mutations in human cancers
Vinagre, João; Almeida, Ana; Pópulo, Helena; Batista, Rui; Lyra, Joana; Pinto, Vasco; Coelho, Ricardo; Celestino, Ricardo; Prazeres, Hugo; Lima, LuísReactivation of telomerase has been implicated in human tumorigenesis, but the underlying mechanisms remain poorly understood. Here we report the presence of recurrent somatic mutations in the TERT promoter in cancers of the central nervous system (43%), bladder (59%), thyroid (follicular cell-derived, 10%) and skin (melanoma, 29%). In thyroid cancers, the presence of TERT promoter mutations (when occurring tog...
Impact of EGFR genetic variants on glioma risk and patient outcome
Costa, Bruno Marques; Pereira, Marta Viana; Fernandes, Ricardo; Costa, S.; Linhares, Paulo; Vaz, Rui; Pinheiro, Céline; Lima, Jorge; Soares, PaulaB.M. Costa and M. Viana-Pereira contributed equally to this work; The authors thank the Immunochemotherapy Department of Hospital S. Marcos, and Clinica Laboratorial Dr. Edgar Botelho Moniz, S. Tirso, Portugal, for their helpful assistance in the management of controls ; BACKGROUND: The epidermal growth factor receptor (EGFR) regulates important cellular processes and is frequently implicated in human tumors. ...
Prognostic value of MGMT promoter methylation in glioblastoma patients treated ...
Costa, Bruno Marques; Caeiro, Cláudia; Guimarães, Inês; Martinho, Olga; Jaraquemada, Teresa; Augusto, Isabel; Castro, Lígia; Osório, LígiaGlioblastoma (GBM) is the most common and aggressive primary brain tumor. The identification of novel molecular prognostic markers of GBM has recently been an area of great interest in neuro-oncology. The methylation status of the MGMT gene promoter is currently a promising molecular prognostic marker, but some controversial data have precluded its clinical use. We analyzed MGMT methylation by methylation-speci...
TP53 codon 72 polymorphism in susceptibility, overall survival, and adjuvant th...
Lima-Ramos, Vítor; Pacheco-Figueiredo, Luís; Costa, Sandra Maria Araújo da; Pardal, Fernando; Silva, Ana; Amorim, Júlia; Lopes, José Manuel; Reis, R. M.TP53 is a key tumor suppressor gene that encodes a transcriptional factor involved in several cellular mechanisms, including growth arrest, DNA repair, and induction of apoptosis. In addition to TP53 gene mutations, a common polymorphism, Arg72Pro, has been involved in the carcinogenesis process. The Pro72 variant has been associated with a slower induction of apoptosis and may influence the risk of cancer deve...
Analysis of EGFR Overexpression, EGFR gene amplification and the EGFRvIII Mutat...
Viana, Marta Pereira; Lopes, José M.; Little, Suzie; Milanezi, Fernanda; Basto, Diana; Pardal, Fernando; Jones, C.; Reis, R. M.Background: Patients with malignant gliomas do not respond to any current therapy. Epidermal growth factor receptor (EGFR) controls several oncogenic processes, being frequently up-regulated in gliomas due to overexpression, gene amplification and gene mutation. EGFR inhibitors are being tried in gliomas, yet the molecular determinants of therapeutic response are unclear. Materials and Methods: EGFR overexpress...
Association between functional EGF+61polymorphism and glioma risk
Costa, Bruno Marques; Ferreira, Paula; Costa, Sandra Maria Araújo da; Canedo, Paulo; Oliveira, Pedro; Silva, Ana; Pardal, Fernando; Suriano, SurianoEpidermal growthf actor (EGF) plays a critical role in cancer. A polymorphism in the EGF gene (EGF+61) may influence its expression and contribute to cancer predisposition and aggressiveness. In the present study, we aimed to elucidate the role of EGF+61in glioma susceptibility and prognosis. Experimental Design:A case-control study involving197 glioma patients and 570 controlswas done. Univariate and multivari...
Mutation analysis of B-RAF gene in human gliomas
Basto, Diana; Trovisco, Vítor; Lopes, José M.; Martins, Albino; Pardal, Fernando; Soares, Paula; Reis, R. M.The RAS/RAF/MEK/ERK kinase pathway is pivotal in the transduction of mitogenic stimuli from activated growth factor receptors, which regulates cell proliferation, survival, and differentiation. Up-regulation of this pathway due to RAS mutations is found in approximately 30% of human tumors. Recently, activating mutations of B-RAF were identified in a large proportion of human cancers. Gliomas are the most frequ...
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