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 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 Transcriptome analysis discloses dysregulated genes in normal appearing tumor-adjacent thyroid tissues from patients with papillary thyroid carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Huiling He ◽  
Sandya Liyanarachchi ◽  
Wei Li ◽  
Daniel F. Comiskey ◽  
Pearlly Yan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Transcriptome Analysis ◽  
Cellular Response ◽  
Molecular Characteristics ◽  
Cancer Genes ◽  
Papillary Thyroid

AbstractPapillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. The molecular characteristics of histologically normal appearing tissue adjacent to the tumor (NAT) from PTC patients are not well characterized. The aim of this study was to characterize the global gene expression profile of NAT and compare it with those of normal and tumor thyroid tissues. We performed total RNA sequencing with fresh frozen thyroid tissues from a cohort of three categories of samples including NAT, normal thyroid (N), and PTC tumor (T). Transcriptome analysis shows that NAT presents a unique gene expression profile, which was not associated with sex or the presence of lymphocytic thyroiditis. Among the differentially expressed genes (DEGs) of NAT vs N, 256 coding genes and 5 noncoding genes have been reported as cancer genes involved in cell proliferation, apoptosis, and/or tumorigenesis. Bioinformatics analysis with Ingenuity Pathway Analysis software revealed that “Cancer, Organismal Injury and Abnormalities, Cellular Response to Therapeutics, and Cellular Movement” were major dysregulated pathways in the NAT tissues. This study provides improved insight into the complexity of gene expression changes in the thyroid glands of patients with PTC.

scholarly journals Differences in Gene Expression Profile of Primary Tumors in Metastatic and Non-Metastatic Papillary Thyroid Carcinoma—Do They Exist?

2020 ◽  
Vol 21 (13) ◽  
pp. 4629
Author(s):  
Sylwia Szpak-Ulczok ◽  
Aleksandra Pfeifer ◽  
Dagmara Rusinek ◽  
Malgorzata Oczko-Wojciechowska ◽  
Malgorzata Kowalska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Molecular Mechanisms ◽  
Group Analysis ◽  
Independent Set ◽  
Gene Set Enrichment Analysis ◽  
Papillary Thyroid ◽  
Primary Tumors ◽  
Gene Group

Molecular mechanisms of distant metastases (M1) in papillary thyroid cancer (PTC) are poorly understood. We attempted to analyze the gene expression profile in PTC primary tumors to seek the genes associated with M1 status and characterize their molecular function. One hundred and twenty-three patients, including 36 M1 cases, were subjected to transcriptome oligonucleotide microarray analyses: (set A—U133, set B—HG 1.0 ST) at transcript and gene group level (limma, gene set enrichment analysis (GSEA)). An additional independent set of 63 PTCs, including 9 M1 cases, was used to validate results by qPCR. The analysis on dataset A detected eleven transcripts showing significant differences in expression between metastatic and non-metastatic PTC. These genes were validated on microarray dataset B. The differential expression was positively confirmed for only two genes: IGFBP3, (most significant) and ECM1. However, when analyzed on an independent dataset by qPCR, the IGFBP3 gene showed no differences in expression. Gene group analysis showed differences mainly among immune-related transcripts, indicating the potential influence of tumor immune infiltration or signal within the primary tumor. The differences in gene expression profile between metastatic and non-metastatic PTC, if they exist, are subtle and potentially detectable only in large datasets.

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.

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
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