DICER1 mutations in Bethesda category II, III, and IV thyroid nodules: A mutually exclusive relationship with BRAFV600E mutation

Abstract

Background

This study aimed to investigate the prevalence and cytological features of Dicer 1, Ribonuclease III (DICER)-mutant fine-needle aspiration (FNA) specimens in thyroid nodules classified as Bethesda II, III, and IV categories. The authors also sought to explore the relationship between DICER1 and BRAF^V600E mutations in Bethesda III thyroid nodules.

Methods

The authors collected a series of consecutive FNA cases diagnosed as Bethesda category II, III, and IV from a medical center over the course of 1 year. DICER1 exons 24 and 25 and TERT promoter mutations were detected by Sanger sequencing in all cases, and BRAF^V600E mutations were detected by amplification refractory mutation system PCR in Bethesda III and IV cases.

Results

A total of 899 patients were included in the study. DICER1 mutations were identified in 52 patients: 20 in Bethesda category II (6.2%, 20 of 322), 25 in Bethesda category III (4.9%, 25 of 510), and seven in Bethesda category IV (10.4%, 7 of 67). Among the 510 Bethesda III FNA samples, 76 harbored the BRAF^V600E mutation and 25 harbored DICER1 mutations. BRAF^V600E and DICER1 mutations were mutually exclusive. In Bethesda category II and III cases, patients with DICER1-mutant nodules were younger and had larger nodule volumes compared to those without DICER1 mutations. All DICER1-mutant Bethesda III FNAs were classified as atypia of undetermined significance (AUS)-other. TERT promoter mutations (c. -118G>T and c. -144 C>T) were identified in two FNA samples.

Conclusion

The findings of this study suggest that DICER1-mutant nodules are unlikely to be BRAF-mutant carcinomas. Further study of the molecular characteristics of DICER1-mutant FNAs will contribute to more accurate cytological diagnosis.