Wasserman JD, et al. - The prevalence of DICER1 variants in pediatric papillary thyroid carcinoma (PTC) was investigated, particularly in tumors without conventional PTC oncogenic alterations. DICER1 was recognized as a driver of pediatric thyroid nodules. A distinct class of low-risk malignancies may be represented by DICER1-mutated PTC. Researchers recommended including DICER1 sequencing and gene dosage determination in molecular analysis of pediatric thyroid specimens, given the incidence of variants in children.

Methods

• This study included patients (N = 40) who underwent partial or total thyroidectomy and who were < 18 years of age at the time of surgery.
• For 40 consecutive thyroidectomy specimens (30 malignant, 10 benign), genotyping was performed for 17 PTC-associated variants as was full sequencing of the exons and exon-intron boundaries of DICER1.

Results

• In 12 of 30 (40%) PTCs, conventional alterations were found (five BRAF^V600E, three RET/PTC1, four RET/PTC3).
• They identified pathogenic DICER1 variants in 3 of 30 (10%) PTCs and in 2 of 10 (20%) benign nodules, all of which were shown to lack conventional alterations and did not recur during follow-up.
• They also noted that 3 of 18 (16.7%) PTCs were constituted by DICER1 alterations without conventional alterations.
• Findings demonstrated that the three DICER1-mutated carcinomas each had two somatic DICER1 alterations, whereas they noted that two follicular-nodular lesions arose in those with germline DICER1 mutations and harbored characteristic second somatic RNase IIIb “hotspot” mutations.