scholarly journals Clinicopathological Significance of BRAF (V600E), NRAS (Q61K) and TERT (C228T, C250T and SNP Rs2853669) Mutations in Bulgarian Papillary Thyroid Carcinoma Patients

2021 ◽  
Vol 48 (1) ◽  
pp. 1-8
Author(s):  
K. Vidinov ◽  
R. Dodova ◽  
P. Mitev ◽  
A. Mitkova ◽  
I. Dimitrova ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Genome Stability ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Single Nucleotide ◽  
Clinicopathological Significance ◽  
Present Pilot Study

Abstract Introduction: Thyroid carcinoma is the most common endocrine cancer. Some somatic mutations in genes (BRAF, NRAS and TERT) involved in key signaling pathways and genome stability have been recently identified to play an important role in its development. Very little research has been done on their frequency and clinical relevance in Bulgarian patients with papillary thyroid cancer (PTC). This study is focused on investigating somatic mutation frequency in Bulgarian patients with PTC and their association with clinicopathologic features. Material and Methods: The study included 50 PTC from Bulgarian patients analyzed for mutations in BRAF (V600E), NRAS (Q61K), single nucleotide polymorphism (SNP) rs2853669 and TERT (C228T and C250T) genes by Sanger sequencing. The results were interpreted using Benchling and SeqScape software, and statistical analysis performed with SPSS. Results: In the studied PTC group BRAF(V600E) and TERT (C228T) mutations were found with frequency of 24% and 2%, respectively. Co-occurrence of both mutations was found in 1 patient (2%). The mutations Q61K (NRAS), and C250T (TERT) were not detected. The SNP rs2853669 was found in 18 patients (52.9%). Correlation analysis with the clinical characteristics of the patients revealed statistically significant association with larger size of the tumor for BRAF(V600E) and smaller tumor size for rs2853669. Conclusion: In the present pilot study, we found that BRAF(V600E) and rs2853669 in TERT are common among PCT patients. While the presence of BRAF V600E mutation was associated with large tumors, the presence of rs2853669 in TERT was found in the majority of PCT below 2 cm. More extensive molecular genetic analysis of TERT, BRAF or RAS mutations in larger sample is needed to further elucidate the clinically important diagnostic and prognostic biomarkers for thyroid cancer.

scholarly journals Expression of B-type RAF V600E in Thyroid Carcinoma and its Association with Histological Type

2021 ◽  
Author(s):  
Sonia Kumari ◽  
Turuvekere Narayanrao Suresh ◽  
SM Azeem Mohiyuddin
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Tumour Size ◽  
Extrathyroidal Extension ◽  
Braf V600e Mutation ◽  
Histological Type ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Thyroid Malignancy ◽  
Clinical Records

Introduction: Thyroid cancer is one of the most common cancers amongst all endocrine cancers. Incidence of thyroid malignancy is about 3-4% of all malignancy in India and 80% of thyroid malignancy belongs to Papillary Thyroid Carcinoma (PTC). Factors affecting the prognosis of PTC include patient’s gender, age, histological findings, tumour size, lymph node metastasis, extrathyroidal extension, and remote metastasis. Presence of B-type RAF V600E (BRAF V600E) mutation in thyroid carcinoma patients tends to present with more aggressive clinicopathological behaviours of PTC, prompting more aggressive radioiodine treatment. Aim: To find out the frequency of occurrence and expression of BRAF V600E mutation by Immunohistochemistry (IHC) in thyroid cancer and its association with histological type and Tumour Nodes Metastases (TNM) Staging. Materials and Methods: The present observational retrospective study included patients treated for thyroid carcinoma between January 2014 to February 2019 at RL Jalappa hospital and Research centre, Kolar, Karnataka, India. The IHC was done with rabbit monoclonal anti-BRAF V600E antibody IgG Clone RM8 (VE1). Clinical records, Fine Needle Aspiration Cytology (FNAC) diagnosis were analysed for 45 thyroid carcinoma cases. Immunopositivity was scored positive when unambiguous clear cytoplasmic staining for the antibody was observed in tumour cells. Categorical data was presented in the form of frequencies and proportions and continuous data was presented as mean and standard deviation. The t-test were applied to find out the difference in means among the groups. The p-value <0.05 was considered statistically significant. Results: Out of total 45 cases, 18 were classical PTC, 18 were Follicular Variant of Papillary Thyroid Cancer (FV-PTC), 4 were micropapillary carcinomas, 3 were Follicular carcinomas, 1 was Oncocytic variant of PTC and 1 undifferentiated thyroid carcinoma. Out of total 45 cases, 33 cases (73%) were found to be BRAF V600E positive and 12 (26%) were negative for BRAF V600E. Out of the total 33 BRAF V600E positive cases, 19 cases showed strong staining, 14 cases showed moderately positive staining. Conclusion: The PTC is the most frequent type of thyroid carcinoma amongst all the sub-types. BRAF V600E expression is commonly seen in higher tumour size (T3, T4) and classical PTC. Tumours with extrathyroidal extension and capsular invasion showed strong positivity.

A mouse model of BRAF V600E mutated papillary thyroid cancer imitating sporadic conditions

2018 ◽  
Author(s):  
Iva Jakubikova ◽  
Elin Schoultz ◽  
Ellen Johansson ◽  
Shawn Liang ◽  
Konrad Patyra ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Mouse Model ◽  
Papillary Thyroid Cancer ◽  
Braf V600e ◽  
Papillary Thyroid

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.

scholarly journals Analysis of the Role of FRMD5 in the Biology of Papillary Thyroid Carcinoma

2021 ◽  
Vol 22 (13) ◽  
pp. 6726
Author(s):  
Agata M. Gaweł ◽  
Maciej Ratajczak ◽  
Ewa Gajda ◽  
Małgorzata Grzanka ◽  
Agnieszka Paziewska ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Endocrine System ◽  
Metastatic Potential ◽  
Multidrug Resistant ◽  
Thyroid Tumor ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Spheroid Formation

Background: Thyroid carcinoma (TC) is the most common endocrine system malignancy, and papillary thyroid carcinoma (PTC) accounts for >80% of all TC cases. Nevertheless, PTC pathogenesis is still not fully understood. The aim of the study was to elucidate the role of the FRMD5 protein in the regulation of biological pathways associated with the development of PTC. We imply that the presence of certain genetic aberrations (e.g., BRAF V600E mutation) is associated with the activity of FRMD5. Methods: The studies were conducted on TPC1 and BCPAP (BRAF V600E) model PTC-derived cells. Transfection with siRNA was used to deplete the expression of FRMD5. The mRNA expression and protein yield were evaluated using RT-qPCR and Western blot techniques. Proliferation, migration, invasiveness, adhesion, spheroid formation, and survival tests were performed. RNA sequencing and phospho-kinase proteome profiling were used to assess signaling pathways associated with the FRMD5 expressional status. Results: The obtained data indicate that the expression of FRMD5 is significantly enhanced in BRAF V600E tumor specimens and cells. It was observed that a drop in intracellular yield of FRMD5 results in significant alternations in the migration, invasiveness, adhesion, and spheroid formation potential of PTC-derived cells. Importantly, significant divergences in the effect of FRMD5 depletion in both BRAF-wt and BRAF-mutated PTC cells were observed. It was also found that knockdown of FRMD5 significantly alters the expression of multidrug resistant genes. Conclusions: This is the first report highlighting the importance of the FRMD5 protein in the biology of PTCs. The results suggest that the FRMD5 protein can play an important role in controlling the metastatic potential and multidrug resistance of thyroid tumor cells.

Effect of Sentinel Node Biopsy in Clinically N0, BRAF V600E–Mutated, Small Papillary Thyroid Carcinoma

2019 ◽  
Vol 44 (5) ◽  
pp. 359-364 ◽  
Author(s):  
Marco Puccini ◽  
Gianpiero Manca ◽  
Carlo Maria Neri ◽  
Giuseppe Boni ◽  
Virginia Coli ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Sentinel Node ◽  
Sentinel Node Biopsy ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Node Biopsy

scholarly journals Quantification of BRAF V600E alleles predicts papillary thyroid cancer progression

2014 ◽  
Vol 21 (6) ◽  
pp. 891-902 ◽  
Author(s):  
Min-Hee Kim ◽  
Ja Seong Bae ◽  
Dong-Jun Lim ◽  
Hyoungnam Lee ◽  
So Ra Jeon ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Progression ◽  
Tumour Size ◽  
External Validation ◽  
Allelic Frequency ◽  
The Cancer Genome Atlas ◽  
Braf V600e ◽  
Validation Dataset ◽  
Papillary Thyroid ◽  
Additional Information

The BRAF V600E mutation is the most common genetic alteration in thyroid cancer. However, its clinicopathological significance and clonal mutation frequency remain unclear. To clarify the inconsistent results, we investigated the association between the allelic frequency of BRAF V600E and the clinicopathological features of classic papillary thyroid carcinoma (PTC). Tumour tissues from two independent sets of patients with classic PTC were manually microdissected and analysed for the presence or absence of the BRAF mutation and the mutant allelic frequency using quantitative pyrosequencing. For external validation, the Cancer Genome Atlas (TCGA) data were analysed. The BRAF V600E mutation was found in 264 (82.2%) out of 321 classic PTCs in the training set. The presence of BRAF V600E was only associated with extrathyroidal extension and the absence of thyroiditis. In BRAF V600E-positive tumours, the mutant allelic frequency varied from 8 to 41% of the total BRAF alleles (median, 20%) and directly correlated with tumour size and the number of metastatic lymph nodes. Lymph node metastases were more frequent in PTCs with a high (≥20%) abundance of mutant alleles than in those with a low abundance of mutant alleles (P=0.010). These results were reinforced by validation dataset (n=348) analysis but were not reproduced in the TCGA dataset. In a population with prevalent BRAF mutations, quantitative analysis of the BRAF mutation could provide additional information regarding tumour behaviour, which is not reflected by qualitative analysis. Nonetheless, prospective studies are needed before the mutated allele percentage can be considered as a prognostic factor.

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