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. 2024 Sep 17:68:e240067.
doi: 10.20945/2359-4292-2024-0067. eCollection 2024.

Follicular cell-derived thyroid carcinomas harboring novel genetic BRAFNON-V600E mutations: real-world data obtained using a multigene panel

Juliana Lima von Ammon  1 , Gabriel Jeferson Rodríguez Machado  1 , Rafael Reis Campos da Matta  1 , Ana Clara Telles  1 , Fabiane Carrijo  1 , Bruno Alexsander França Dos Santos  2 , Juliana Cabral Duarte Brandão  3 , Thiago Magalhães da Silva  4 , Fabio Hecht  5 , Gabriel Avela Colozza-Gama  6 , Julia Helena Tezzei  6 , Janete Maria Cerutti  6 , Helton Estrela Ramos  1   2
Affiliations

Follicular cell-derived thyroid carcinomas harboring novel genetic BRAFNON-V600E mutations: real-world data obtained using a multigene panel

Juliana Lima von Ammon et al. Arch Endocrinol Metab. .

Abstract

Objectives: To assess the molecular profile of follicular cell-derived thyroid carcinomas (FCDTCs) and correlate the identified mutations with the clinical and pathological features of the affected patients.

Materials and methods: Cross-sectional study of tumor samples from 100 adult patients diagnosed with FCDTC between 2010 and 2019. The patients' clinical and pathological data were collected. Genomic DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tumors using the ReliaPrep FFPE gDNA Miniprep System. Genotyping of target genomic regions (KRAS, NRAS, BRAF, EGFR, and PIK3CA) was performed using the AmpliSeq panel, while sequencing was performed on the iSeq 100 platform.

Results: The patients' mean age was 39 years. In all, 82% of the tumors were classic papillary thyroid carcinomas. Overall, 54 (54%) tumor samples yielded satisfactory results on next-generation sequencing (NGS), of which 31 harbored mutations. BRAF gene mutations were the most frequent, with the BRAF V600E mutation present in 10 tumors. Seven tumors had BRAF NON-V600E mutations not previously described in FCDTCs (G464E, G464R, G466E, S467L, G469E, G596D, and the T599Ifs*10 deletion) but described in other types of cancer (i.e., skin/melanoma, lung, colorectal, and others). One tumor had a previously reported BRAF A598V mutation. EGFR gene mutations were found in 16 (29%) and KRAS or NRAS alterations in 8 (14%) of the 54 tumors analyzed.

Conclusion: We described herein seven non-hotspot/novel variants in the BRAF gene, highlighting their potential role in expanding our understanding of FCDTC genetics.

Keywords: BRAFV600E; Thyroid cancer; mutation; next-generation sequencing; papillary thyroid carcinoma.

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Conflict of interest statement

Disclosure: no potential conflict of interest relevant to this article was reported.

Figures

Figure 1
Figure 1. Relationship between (A) paraffin block age (0-3, 3-7, and >7 years) and (B) tumor size (≥2 and <2 cm) with the success/failure rate of next-generation sequencing (NGS). The success rate was significantly lower in tumors < 2 cm.
Figure 2
Figure 2. Oncogrid showing the distribution of the oncogenic genetic alterations identified and the patients’ clinical and pathological characteristics. Abbreviations: CPTC, classic papillary thyroid carcinoma; IFC, invasive follicular carcinoma; IFVPTC, infiltrative follicular variant of papillary thyroid carcinoma; SVPTC, solid variant of papillary thyroid carcinoma; OVPTC, oncocytic variant of papillary thyroid carcinoma; EFVPTC, noninvasive encapsulated follicular variant of papillary thyroid carcinoma; MCTC, cribriform-morular thyroid carcinoma.
Figure 3
Figure 3. BRAF domain structure and location of the hotspot mutations found in the study. Abbreviations: RBD, RAS-binding domain; CRD, cysteine-rich domain.
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