Prevalence and phenotypic correlations of EIF1AX mutations in thyroid nodules

Area of Science:

• Oncology
• Genetics
• Endocrinology

Background:

• EIF1AX gene mutations are recently identified in papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC).
• The prevalence and significance of EIF1AX mutations in other thyroid lesions remain largely unknown.

Purpose of the Study:

• To investigate the occurrence of EIF1AX mutations in various thyroid tumors, hyperplastic nodules, and fine-needle aspiration (FNA) samples.
• To determine the association of EIF1AX mutations with different thyroid cancer types and benign conditions.

Main Methods:

• Sanger sequencing and next-generation sequencing (ThyroSeq v.2) were used to analyze EIF1AX mutations in exons 2, 5, and 6.
• A total of 266 surgically removed thyroid tumors/nodules and 647 indeterminate FNA samples were analyzed.

Main Results:

• EIF1AX mutations were detected in PTC (2.3%), ATC (25%), follicular adenomas (7.4%), and hyperplastic nodules (1.3%).
• The A113_splice mutation was the most frequent, observed in all four carcinoma cases, often coexisting with RAS mutations.
• In FNA samples, EIF1AX mutations predicted approximately a 20% risk of malignancy, higher with A113_splice or coexisting RAS mutations.

Conclusions:

• EIF1AX mutations are present in both thyroid carcinomas and benign nodules.
• The A113_splice mutation is a common hotspot, and its detection in FNA samples is a significant indicator of potential thyroid cancer.
• EIF1AX mutations, especially when combined with RAS mutations, can refine cancer risk assessment in indeterminate thyroid FNA cases.