Please use this identifier to cite or link to this item: http://hdl.handle.net/10216/109554
Author(s): Melo, M
Gaspar da Rocha, A
Batista, R
Vinagre, J
Martins, MJ
Costa, G
Ribeiro, C
Carilho, F
Leite, V
Lobo, C
Cameselle-Teijeiro, JM
Cavadas, B
Pereira, L
Sobrinho-Simões, M
Soares, P
Title: TERT, BRAF and NRAS in primary thyroid cancer and metastatic disease
Publisher: Oxford University Press
Issue Date: 2017
Abstract: Context: Little is known about the frequency of key mutations in thyroid cancer metastases and its relationship with the primary tumor genotype. Objectives: To evaluate the frequency of TERT promoter (TERTp), BRAF, and NRAS mutations in metastatic thyroid carcinomas, analyzing primary thyroid tumors, lymph node metastases (LNMs), and distant metastases. Design and Patients: Mutation analysis was performed in 437 tissue samples from 204 patients, mainly with papillary thyroid carcinomas (PTCs; n = 180), including 196 LNMs and 56 distant metastases. All the distant metastases included corresponded to radioiodine-refractory metastatic tissue. Results: We found the following mutation frequency in primary PTCs, LNMs, and distant metastases, respectively: TERTp: 12.9%, 10.5%, and 52.4%; BRAF: 44.6%, 41.7%, and 23.8%; and NRAS: 1.2%, 1.3%, and 14.3%. There was a significant concordance between the primary tumor genotype and the corresponding LNM for all the genes, in particular BRAF-mutated PTC. The overall concordance between primary tumors and respective distant metastases was low. In the group of patients with PTCs, we found a high frequency of TERTp mutations and a low frequency of BRAF mutations in distant metastases, in comparison with the paired primary tumors. When present in distant metastases, BRAF mutations frequently coexisted with TERTp mutations. Conclusions: When the genotype of primary tumors is compared with the genotype of LNMs, the concordance is high for all the genes studied. On the other hand, distant metastases show an enrichment in TERTp mutations and a decrease in BRAF mutations. TERTp mutations may play a role in distant metastases.
Subject: Adult
Aged
Carcinoma/genetics
Carcinoma/secondary
Carcinoma Papillary
DNA Mutational Analysis
Female
GTP Phosphohydrolases/genetics
Genotype
Humans
Lymph Nodes/pathology
Lymphatic Metastasis
Male
Membrane Proteins/genetics
Middle Aged
Mutation
Neoplasm Metastasis
Promoter Regions Genetic/genetics
Proto-Oncogene Proteins B-raf/genetics
Telomerase/genetics
Thyroid Neoplasms/genetics
Thyroid Neoplasms/pathology
Thyroid Neoplasms/secondary
URI: http://hdl.handle.net/10216/109554
Source: The Journal of Clinical Endocrinology & Metabolism, vol. 102(6), p. 1898-1907
Related Information: info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F81940%2F2011/PT
Document Type: Artigo em Revista Científica Internacional
Rights: restrictedAccess
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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