Differences in Mutational Profile between Follicular Thyroid Carcinoma and Follicular Thyroid Adenoma Identified Using Next Generation Sequencing

• Main Authors: Martyna Borowczyk, Ewelina Szczepanek-Parulska, Szymon Dębicki, Bartłomiej Budny, Frederik A. Verburg, Dorota Filipowicz, Barbara Więckowska, Małgorzata Janicka-Jedyńska, Lidia Gil, Katarzyna Ziemnicka, Marek Ruchała
• Format: Article
• Language: English
• Published: MDPI AG 2019-06-01
• Series: International Journal of Molecular Sciences
• Subjects: follicular thyroid cancer; follicular thyroid adenoma; next-generation sequencing; whole-genome studies; genetics
• Online Access: https://www.mdpi.com/1422-0067/20/13/3126

We aimed to identify differences in mutational status between follicular thyroid adenoma (FTA) and follicular thyroid cancer (FTC). The study included 35 patients with FTA and 35 with FTC. DNA was extracted from formalin-fixed paraffin-embedded (FFPE) samples from thyroidectomy. Next-generation sequencing (NGS) was performed with the 50-gene Ion AmpliSeq Cancer Hotspot Panel v2. Potentially pathogenic mutations were found in 14 (40%) FTA and 24 (69%) FTC patients (OR (95%CI) = 3.27 (1.22&#8722;8.75)). The number of mutations was higher in patients with FTC than FTA (<i>p</i>-value = 0.03). <i>SMAD4</i> and <i>STK11</i> mutations were present only in patients with FTA, while defects in <i>FBXW7</i>, <i>JAK3</i>, <i>KIT</i>, <i>NRAS</i>, <i>PIK3CA</i>, <i>SMARCB1</i>, and <i>TP53</i> were detected exclusively in FTC patients. <i>TP53</i> mutations increased the risk of FTC; OR (95%CI) = 29.24 (1.64&#8722;522.00); <i>p</i>-value = 0.001. <i>FLT3</i>-positivity was higher in FTC than in the FTA group (51.4% vs. 28.6%; <i>p</i>-value = 0.051). The presence of <i>FLT3</i> and <i>TP53</i> with no <i>RET</i> mutations increased FTC detectability by 17.1%, whereas the absence of <i>FLT3</i> and <i>TP53</i> with a presence of <i>RET</i> mutations increased FTA detectability by 5.7%. <i>TP53</i> and <i>FLT3</i> are candidate markers for detecting malignancy in follicular lesions. The best model to predict FTA and FTC may consist of <i>FLT3</i>, <i>TP53</i>, and <i>RET</i> mutations considered together.