Document details
TERT, BRAF, and NRAS in primary thyroid cancer and metastatic disease(Article)(Open Access)
Retrieving additional authors...
- aI3S Instituto de Investigaçao e Inovaçao EmSaúde, Porto, 4200-135, Portugal
- bInstitute OfMolecular Pathology and Immunology, University of Porto, Porto, 4200-135, Portugal
- cDepartment of Endocrinology, Diabetes, and Metabolism, CentroHospitalar EUniversitá Rio DeCoimbra, Praceta Mota Pinto, Coimbra, 3000-075, Portugal
- dUnit of Endocrinology, Faculty of Medicine, University of Coimbra, Coimbra, 3000-075, Portugal
- ePublic Health Unit, ACeS Baixo Mondego, Coimbra, 3040-006, Portugal
- fMedical Faculty, University of Porto, Porto, 4200-319, Portugal
- gInstitute of Biomedical Sciences of Abel Salazar, University of Porto, Porto, 4050-313, Portugal
- hDepartment of Pathology, Centro Hospitalar e Universitário de Coimbra, Coimbra, 3000-075, Portugal
- iDepartment of Nuclear Medicine, Centro Hospitalar e Universitário de Coimbra, Coimbra, 3000-075, Portugal
- jUnit for Investigation of Molecular Pathobiology, Portuguese Institute of Oncology-Lisbon Center, Lisbon, 1099-023, Portugal
- kFaculty of Medical Sciences, University of Lisbon, Lisbon, 1169-056, Portugal
- lDepartment of Endocrinology, Portuguese Institute of Oncology-Lisbon Center, Lisbon, 1099-023, Portugal
- mDepartment of Pathology, Portuguese Institute of Oncology-Porto Center, Porto, 4200-072, Portugal
- nDepartment of Pathology, Clinical University Hospital, Servizo Galego de Saúde (SERGAS), Medical Faculty, University of Santiago de Compostela, Santiago de Compostela, 15706, Spain
- oDepartment of Pathology and Oncology, Medical Faculty, University of Porto, Porto, 4200-319, Portugal
- pDepartment of Pathology, Hospital Sao Joao, Porto, 4200-319, Portugal
Retrieving additional affiliations...
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 thyroidcarcinomas, analyzingprimarythyroidtumors, lymphnodemetastases (LNMs),anddistant metastases. Design and Patients:Mutation analysiswas performed in 437 tissue samples from204 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:Wefound 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. Copyright © 2017 Endocrine Society.
Indexed keywords
| EMTREE drug terms: | B Raf kinaseiodine 131mitogen activated protein kinasetelomerase reverse transcriptaseB Raf kinaseBRAF protein, humanguanosine triphosphatasemembrane proteinNRAS protein, humantelomeraseTERT protein, human |
|---|---|
| EMTREE medical terms: | adultArticleBRAF genecontrolled studydistant metastasisfemalegenegene mutationgenotypehumanhuman tissuelymph node metastasismajor clinical studymalemetastasismutation rateNRAS geneprimary tumorpriority journalpromoter regionTERT genethyroid cancerthyroid follicular carcinomathyroid papillary carcinomatumor growthagedcarcinomadna mutational analysisgeneticslymph nodelymph node metastasismetastasismiddle agedmutationpathologysecondarythyroid tumor |
| MeSH: | AdultAgedCarcinomaDNA Mutational AnalysisFemaleGenotypeGTP PhosphohydrolasesHumansLymph NodesLymphatic MetastasisMaleMembrane ProteinsMiddle AgedMutationNeoplasm MetastasisPromoter Regions, GeneticProto-Oncogene Proteins B-rafTelomeraseThyroid Neoplasms |
Chemicals and CAS Registry Numbers:
iodine 131, 10043-66-0, 15124-39-7; mitogen activated protein kinase, 142243-02-5; telomerase reverse transcriptase, 120178-12-3; guanosine triphosphatase, 9059-32-9;
BRAF protein, human; GTP Phosphohydrolases; Membrane Proteins; NRAS protein, human; Proto-Oncogene Proteins B-raf; Telomerase; TERT protein, human
- ISSN: 0021972X
- CODEN: JCEMA
- Source Type: Journal
- Original language: English
- DOI: 10.1210/jc.2016-2785
- PubMed ID: 28323937
- Document Type: Article
- Publisher: Endocrine Society
Melo, M.; Department of Endocrinology, Diabetes, and Metabolism, CentroHospitalar EUniversitá Rio DeCoimbra, Praceta Mota Pinto, Coimbra, Portugal;
© Copyright 2017 Elsevier B.V., All rights reserved.
Cited by 26 documents
Huang, M.
, Yan, C.
, Xiao, J.
(2019) Diagnostic Pathology
(2019) Diagnostic Pathology
Meng, Z.
, Matsuse, M.
, Saenko, V.
(2019) IUBMB Life
(2019) IUBMB Life
Jeon, M.J.
, Chun, S.M.
, Lee, J.-Y.
(2019) Endocrine
(2019) Endocrine
View details of all 26 citations
{"topic":{"name":"Thyroid Neoplasms; Carcinoma, Papillary; RAS mutations","id":3209,"uri":"Topic/3209","prominencePercentile":97.846756,"prominencePercentileString":"97.847","overallScholarlyOutput":0},"dig":"68ac9dac4bbc3dae5224d16f2c9fe89b946704c20522d8dc04862203c985a1bb"}