Mutation profile of the tall cell variant of papillary thyroid carcinoma: analysis of 5 cases using wide-panel next-generation sequencing
Open Access
- 24 April 2021
- journal article
- Published by Publishing House ABV Press in Head and Neck Tumors (HNT)
- Vol. 11 (1), 78-85
- https://doi.org/10.17650/2222-1468-2021-11-1-78-85
Abstract
The study objective is to analyze the mutation profile of the tall cell variant (TCV) of papillary thyroid carcinoma (PTC).Materials and methods. The main inclusion criteria according to the WHO classification (2017) was PTC composed of at least 30 % of tall cells. Genetic examination was conducted using the FoundationOne CDx assay (USA) with median depth of coverage of >500x. This study included 5 patients (1 man and 4 women) with a mean age of 52.6 years (range: 48-56 years). The tumor size varied between 0.4 x 0.5 cm and 11.0 x 9.0 cm. All patients have undergone surgical treatment: hemithyroidectomy for patient No. 1 with a small tumor (pT1b); thyroidectomy for patient No. 2 (pT3b); extensive thyroidectomy with the removal of paratracheal tissue for patients No. 3, 4, and 5 (No. 3 - pT3bN0; No. 4 - pT3bN1b; No. 5 - pT3bN1b). Three out of the five patients also had adenomatous goiter. The mean follow-up time was 3.4 to 5.2 years.Results. Tumors in all patients were characterized by low mutational load (0 to 4 mutations per 1 million nucleotides (megabase)) and no microsatellite instability. All study participants were found to have p.V600E mutation in the BRAF gene; two patients had c.-124C>T mutation in the promoter region of the TERT gene. All patients carried mutations with unknown clinical significance: p.V562I in the EPHB1 gene (in 2 patients); mutations in the genes AR, CREBBP, EP300, ERCC4, FLT1, IKBKE, JAK2, MAF, MLL2, MST1R, MYC, MYCL1, NTRK2, TSC2 (each mutation registered in one patient). One individual with the largest tumor and the most aggressive disease was found to have amplifications of the BTG2, MAP3K1, SMAD2, and TBX3 genes.Conclusion. In 5 patients analyzed in this study, the mutation profile of TCV PTC was characterized by low mutational load, no microsatellite instability, and presence of p.V600E mutation in the BRAF gene in all cases. Some patients also had c.-124C>T mutation in the TERT gene and p.V562I mutation in the EPHB1 gene.Keywords
This publication has 23 references indexed in Scilit:
- Relationship between BRAF V600E and clinical features in papillary thyroid carcinomaEndocrine Connections, 2019
- Papillary thyroid carcinoma with tall cell features is as aggressive as tall cell variant: a meta-analysisEndocrine Connections, 2018
- Synergistic inhibition of MEK/ERK and BRAF V600E with PD98059 and PLX4032 induces sodium/iodide symporter (NIS) expression and radioiodine uptake in BRAF mutated papillary thyroid cancer cellsThyroid Research, 2018
- Vemurafenib in patients with BRAFV600E-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trialThe Lancet Oncology, 2016
- Redifferentiation of Iodine-Refractory BRAF V600E-Mutant Metastatic Papillary Thyroid Cancer with DabrafenibClinical Cancer Research, 2015
- BRAF Inhibitor Dabrafenib in Patients with Metastatic BRAF-Mutant Thyroid CancerThyroid®, 2015
- Telomerase in differentiated thyroid cancer: Promoter mutations, expression and localizationMolecular and Cellular Endocrinology, 2014
- The BRAFV600E mutation in papillary thyroid microcarcinoma: does the mutation have an impact on clinical outcome?Clinical Endocrinology, 2014
- The association of the BRAFV600E mutation with prognostic factors and poor clinical outcome in papillary thyroid cancerCancer, 2011
- Tall Cell Variant of Papillary Thyroid Carcinoma without Extrathyroid Extension: Biologic Behavior and Clinical ImplicationsThyroid®, 2007