Objectives: Variants in the EIF1AX gene have been reported in malignant as well as benign thyroid nodules and their clinical significance is still unclear due to their low prevalence. The aim of this study was to identify EIF1AX variants in a large cohort of different types of thyroid nodules and to correlate them with clinical and pathological data.
Methods: The study consisted of 904 thyroid nodule samples. The cohort included 577 papillary thyroid carcinomas (PTCs), 16 anaplastic thyroid carcinomas (ATCs), 8 poorly differentiated thyroid carcinomas (PDTCs), 18 follicular thyroid carcinomas (FTCs), 10 oncocytic carcinomas, 35 borderline lesions (e.g., follicular tumor of uncertain malignant potential - FT-UMP), 55 follicular thyroid adenomas (FTA) and 185 benign nodules. DNA isolated from fresh frozen thyroid tissues was used for preparation of libraries using the Nextera XT DNA Library Prep Kit (Illumina, USA) and analyzed using next-generation sequencing (MiSeq, Illumina, USA). Variants in the EIF1AX gene (exons 1, 2, 5, 6) were visualized in Integrative Genomics Viewer (Broad Institute, USA) and evaluated by VarSome platform (Saphetor SA, Switzerland).
Results: EIF1AX gene variants were detected in 18 of 904 thyroid samples (2%) - 2 ATCs, 3 PTCs, 2 FTCs, 2 FTAs, 2 FT-UMPs, 1 oncocytic adenoma and 6 other benign nodules. The most frequent EIF1AX A113_splice variant was found in 6 of 18 (33.3%) positive samples (1 ATC, 2 PTC, 1 FTA, 1 FT-UMP and 1 goiter). Variants in codon 9 (G9R, G9V, G9D) of EIF1AX gene were found in 3 benign nodules and 1 ATC, in which coexisted with variants of TERT, TP53 and NRAS genes. The coexistence of EIF1AX variants with mutations in other genes (5× TERT, 9× RAS 4 × simultaneously) was found in a total of 10 of 18 cases, and often correlated with more aggressive disease. On the other side, 8 EIF1AX-positive samples which did not possess other driver mutations were benign nodules, FTAs or FT-UMPs.
Conclusion: In summary, EIF1AX gene variants were detected in 18 cases. In most cases, the EIF1AX variants co-occurred with known variants of other genes and were associated with more aggressive tumor behavior. In accordance with literature, distinct EIF1AX variants may be related to different types of thyroid tumors and extension of the positive cohort could provide more accurate insight into the understanding of this gene. Supported by AZV NU21-01-00448 and MH CR RVO 00023761.
10 Sep 2022 - 13 Sep 2022