scholarly journals TERT promoter mutations are associated with distant metastases in papillary thyroid carcinoma

2015 ◽  
Vol 172 (4) ◽  
pp. 403-413 ◽  
Author(s):  
Greta Gandolfi ◽  
Moira Ragazzi ◽  
Andrea Frasoldati ◽  
Simonetta Piana ◽  
Alessia Ciarrocchi ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Direct Sequencing ◽  
Distant Metastases ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Mutational Status ◽  
Metastatic Behavior ◽  
Well Differentiated ◽  
Promoter Mutations

ObjectiveTranscriptional activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene were reported at high frequency in aggressive poorly differentiated and anaplastic thyroid cancers. By contrast, the relevance of these mutations in the metastatic behavior of well-differentiated thyroid cancer is still to be defined. The aim of this work was to investigate the frequency ofTERTpromoter mutations in a remarkable cohort of well-differentiated papillary thyroid carcinoma that developed distant metastases (DM-PTCs) and to establish whether these mutations may be predictive of metastatic behavior.DesignWe analyzed the frequency ofTERTpromoter mutations in a group of 43 highly aggressive DM-PTCs. As controls, we analyzed these mutations in a group of 78 PTCs without distant metastases (control-PTCs). The possible correlation betweenTERTpromoter mutations and BRAF V600E mutation was also investigated.MethodsTERTpromoter mutational status was evaluated by direct sequencing of the hotspot harboring the C228T and the C250T mutations.ResultsIn the overall cohort of 121 PTCs analyzed, 17% of cases (21/121) carried a mutation in theTERTpromoter. Noticeably, 33% of DM-PTCs were mutated in theTERTpromoter while only 9% of the control-PTCs showed a mutation in this locus. We also observed a positive association between BRAF V600E andTERTC228T mutations in the cohort of DM-PTCs.ConclusionsThese results indicate thatTERTpromoter mutations are associated with the development of distant metastases in PTCs and may help in predicting aggressive behavior in this type of tumor.

scholarly journals TERT Promoter Mutations and Their Impact on Gene Expression Profile in Papillary Thyroid Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1597 ◽  
Author(s):  
Dagmara Rusinek ◽  
Aleksandra Pfeifer ◽  
Marta Cieslicka ◽  
Malgorzata Kowalska ◽  
Agnieszka Pawlaczek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Distant Metastases ◽  
Gene Set Enrichment Analysis ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Mutational Status

Background: Telomerase reverse transcriptase promoter (TERTp) mutations are related to a worse prognosis in various malignancies, including papillary thyroid carcinoma (PTC). Since mechanisms responsible for the poorer outcome of TERTp(+) patients are still unknown, searching for molecular consequences of TERTp mutations in PTC was the aim of our study. Methods: The studied cohort consisted of 54 PTCs, among them 24 cases with distant metastases. BRAF V600E, RAS, and TERTp mutational status was evaluated in all cases. Differences in gene expression profile between TERTp(+) and TERTp(−) PTCs were examined using microarrays. The evaluation of signaling pathways and gene ontology was based on the Gene Set Enrichment Analysis. Results: Fifty-nine percent (32/54) of analyzed PTCs were positive for at least one mutation: 27 were BRAF(+), among them eight were TERTp(+), and 1 NRAS(+), whereas five other samples harbored RAS mutations. Expression of four genes significantly differed in BRAF(+)TERTp(+) and BRAF(+)TERTp(−) PTCs. Deregulation of pathways involved in key cell processes was observed. Conclusions: TERTp mutations are related to higher PTC aggressiveness. CRABP2 gene was validated as associated with TERTp mutations. However, its potential use in diagnostics or risk stratification in PTC patients needs further studies.

scholarly journals Tall cell papillary thyroid carcinoma: new diagnostic criteria and mutations in BRAF and TERT

2015 ◽  
Vol 22 (3) ◽  
pp. 419-429 ◽  
Author(s):  
Matthias S Dettmer ◽  
Anja Schmitt ◽  
Hans Steinert ◽  
David Capper ◽  
Holger Moch ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Diagnostic Criteria ◽  
Adverse Outcome ◽  
Braf V600e ◽  
Molecular Diagnostic ◽  
Papillary Thyroid ◽  
Tumor Relapse ◽  
Tall Cell ◽  
Promoter Mutations

The tall cell (TC) variant of papillary thyroid carcinoma (PTC) has an unfavorable prognosis. The diagnostic criteria remain inconsistent, and the role of a minor TC component is unclear. Molecular diagnostic markers are not available; however, there are two potential candidates:BRAF V600Eand telomerase reverse transcriptase (TERT) promoter mutations. Using a novel approach, we enriched a collective with PTCs that harbored an adverse outcome, which overcame the limited statistical power of most studies. This enabled us to review 125 PTC patients, 57 of which had an adverse outcome. The proportion of TCs that constituted a poor prognosis was assessed. All of the tumors underwent sequencing forTERTpromoter andBRAFV600Emutational status and were stained with an antibody to detect theBRAFV600Emutation. A 10% cutoff for TCs was significantly associated with advanced tumor stage and lymph node metastasis. Multivariate analysis showed that TCs above 10% were the only significant factor for overall, tumor-specific, and relapse-free survival. Seven percent of the cases had aTERTpromoter mutation, whereas 61% demonstrated aBRAFmutation. The presence of TC was significantly associated withTERTpromoter andBRAFmutations.TERTpredicted highly significant tumor relapse (P<0.001). PTCs comprised of at least 10% TCs are associated with an adverse clinical outcome and should be reported accordingly.BRAFdid not influence patient outcome. Nevertheless, a positive status should encourage the search for TCs.TERTpromoter mutations are a strong predictor of tumor relapse, but their role as a surrogate marker for TCs is limited.

scholarly journals BRAF V600E and TERT Promoter Mutations in Papillary Thyroid Carcinoma in Chinese Patients

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0153319 ◽  
Author(s):  
Jian Sun ◽  
Jing Zhang ◽  
Junliang Lu ◽  
Jie Gao ◽  
Xinyu Ren ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Braf V600e ◽  
Chinese Patients ◽  
Papillary Thyroid ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

scholarly journals Incidence of BRAF V600E mutation in patients with papillary thyroid carcinoma: a single-institution experience

2019 ◽  
Vol 47 (11) ◽  
pp. 5560-5572
Author(s):  
Shoko Kure ◽  
Kousuke Ishino ◽  
Mitsuhiro Kudo ◽  
Ryuichi Wada ◽  
Marie Saito ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Direct Sequencing ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Nippon Medical School ◽  
Dependent Manner ◽  
Papillary Thyroid ◽  
Epithelial Tumor ◽  
Background Population

Objective Papillary thyroid carcinoma (PTC) accounts for 95% of all thyroid carcinomas. PTC is an epithelial tumor characterized by the proliferation of follicular cells with distinctive nuclear features, and is heterogeneous in terms of its carcinogenesis and behavior. PTC has been associated with several genetic abnormalities, of which the BRAF V600E mutation is the most common. However, reported incidences of this mutation have varied depending on the patient background, population size, or methods. In this study, we investigated the incidence of BRAF V600E mutation and its relationships with clinicopathological characteristics in patients with PTC. Methods Surgical specimens were obtained from 40 patients with PTC who underwent surgery at Nippon Medical School Hospital between 2009 and 2017. DNA from exon 15 of the BRAF gene was extracted and amplified by polymerase chain reaction, followed by direct sequencing. Results The frequency of BRAF V600E mutation increased with age. However, there were no correlations between BRAF V600E mutation and other clinicopathological features including sex, Hashimoto disease, family history of thyroid disease, tumor size, pathological T stage, pathological N stage, lymphovascular invasion, extrathyroidal extension, and metastasis. Conclusions This study demonstrated that PTCs harboring the BRAF V600E mutation increased in an age-dependent manner.

scholarly journals Seven-year follow-up of a juvenile female with papillary thyroid carcinoma with poor outcome, BRAF mutation and loss of expression of iodine-metabolizing genes

2008 ◽  
Vol 52 (8) ◽  
pp. 1313-1316 ◽  
Author(s):  
Gisele Oler ◽  
Claudia D. Nakabashi ◽  
Rosa Paula M. Biscolla ◽  
Janete M. Cerutti
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Braf Mutation ◽  
Thyroid Tissue ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Genetic Event ◽  
Mutational Status

BACKGROUND: Recent studies reported that BRAF V600E mutation, the most prevalent genetic event found in papillary thyroid carcinoma, is an independent poor prognostic marker. Additionally, it correlates with a less differentiated tumor stage due to reduced expression of key genes involved in iodine metabolism. We previously described a patient with BRAF V600E mutation in primary tumor and a new mutation (V600E+K601del) in the matched-lymph node metastases. In the present study we report an unusual clinical behavior of PTC and correlate with BRAF mutational status and level of expression of TSHR and NIS. METHODS: Quantitative PCR (qPCR) was used to evaluate the NIS and TSHR level of expression in matched papillary thyroid carcinoma and adjacent normal tissue. RESULTS: In this study, we presented a seven-year follow up of a juvenile papillary thyroid carcinoma patient who had an aggressive tumor harboring BRAF mutation, and failed to conventional therapy. We found a markedly decrease of NIS and TSHR expression in primary PTC compared to adjacent normal thyroid tissue. CONCLUSION: Our findings suggest that BRAF mutational status and decreased NIS and TSHR expression in this patient may reduce radioiodine uptake and lead to a negative response to radioiodine therapy.

scholarly journals Cytologic, histologic and molecular findings of papillary thyroid carcinoma variants, one institution’s experience

2019 ◽  
Vol 9 (2) ◽  
pp. 32
Author(s):  
Nadja K. Falk ◽  
Swarnamala Ratnayaka ◽  
Andrew Sholl ◽  
Krzysztof Moroz ◽  
Tatyana Kalinicheva
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Follicular Variant ◽  
Tert Promoter Mutations ◽  
Patient Prognosis ◽  
One Year ◽  
Promoter Mutations ◽  
Worse Prognosis

Papillary thyroid carcinoma (PTC) has two major types, classic (PTCC) and follicular variant (FVPTC), which correlate with molecular findings and have varying clinical implications. We assessed the cytologic findings and subsequent surgical pathology findings with the molecular mutations in these two groups, including microcarcinomas. Fourty-four patients with PTC resections over a one-year period were retrospectively examined in conjunction with previous cytologic diagnoses. BRAF, NRAS and TERT promoter mutations for the resected specimens were analyzed. Correlation with previous cytology in regard to molecular mutations and tumor size (microcarcinoma) were made. Significantly more BRAF V600E mutations were seen with PTCC, whereas significantly more NRAS mutations were seen with FVPTC. TERT mutations were only seen with PTCC. Molecular studies for thyroid carcninomas are becoming increasingly more common and influence treatment and patient prognosis. BRAF and or TERT mutations are associated with a worse prognosis. NRAS mutations associated with FVPTC and may lead to milder cytologic changes compared to the BRAF- and TERT-driven PTCC.

Mixed histiocytosis with BRAF (V600E) mutation and papillary thyroid carcinoma

2019 ◽  
Author(s):  
Francoise Archambeaud ◽  
Pauline Vital ◽  
Gilles Russ ◽  
Isabelle Pommepuy ◽  
Julien Haroche ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Papillary Thyroid

BRAFV600E MUTATION IN PAPILLARY THYROID CARCINOMA. CLINICAL AND METHODOLOGICAL ASPECTS

2019 ◽  
Vol 65 (1) ◽  
pp. 16-26
Author(s):  
Pavel Rumyantsev ◽  
Petr Nikiforovich ◽  
Andrey Poloznikov ◽  
Andrey Abrosimov ◽  
Vladimir Saenko ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Kinase Inhibitors ◽  
Anaplastic Carcinoma ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Brafv600e Mutation ◽  
Wide Range ◽  
Methodological Aspects

Mutation BRAFV600E is highly specific for papillary thyroid carcinoma. It’s detected in 40-70% of all papillary thyroid carcinoma cases. Moreover this mutation is noticed in anaplastic carcinoma in 40-50%.This fact gives a chance to select patients and provide targeted therapy with multi-kinase inhibitors in cases of unresectable anaplastic carcinoma. The influence of BRAF V600E mutation for response to radioactive iodine therapy requires more evidence-based research. Existing methods for determining the BRAFV600E mutation have different accuracy, availability and cost. Other methodological aspects are also associated with the sample preparation of biological material, the quality of reagents, and the cross-validation of research results. In this review, on the basis of our own experience and literature data, the indications for determining the mutation of the BRAFV600E gene in clinical practice are refined, and a comprehensive comparative analysis of modern research methods has been conducted. This review is focused on a wide range of specialists of different types: oncologists, endocrinologists, radiologists, pathologists, and biologists.

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