DICER1 mutations are frequent in adolescent-onset papillary thyroid carcinoma.

DICER1 mutations are frequent in adolescent-onset papillary thyroid carcinoma.

J Clin Endocrinol Metab. 2018 Feb 21;:

Authors: Wasserman JD, Sabbaghian N, Fahiminiya S, Chami R, Mete O, Acker M, Wu MK, Shlien A, de Kock L, Foulkes WD

Abstract
Context: Papillary thyroid carcinoma (PTC) is a common malignancy in adolescence and is molecularly and clinically distinct from adult PTC. Mutations in the DICER1 gene are associated with thyroid abnormalities including multinodular goitre and differentiated thyroid carcinoma.
Objective: In this study, we sought to characterize the prevalence of DICER1 variants in paediatric PTC, specifically in tumours without conventional PTC oncogenic alterations.
Patients: Patients (n = 40) who underwent partial or total thyroidectomy and who were <18 years of age at the time of surgery were selected.
Design: The forty consecutive thyroidectomy specimens (30 malignant, 10 benign) underwent genotyping for 17 PTC-associated variants, as well as full sequencing of the exons and exon-intron boundaries of DICER1.
Results: Conventional alterations were found in 12/30 (40%) PTCs (5 BRAFV600E, 3 RET/PTC1, 4 RET/PTC3). Pathogenic DICER1 variants were identified in 3/30 (10%) PTCs, and in 2/10 (20%) benign nodules, all of which lacked conventional alterations and did not recur during follow-up. DICER1 alterations thus constituted 3/18 (16.7%) PTCs without conventional alterations. The 3 DICER1-mutated carcinomas each had 2 somatic DICER1 alterations, whereas 2 follicular-nodular lesions arose in those with germline DICER1 mutations and harboured characteristic second somatic RNase IIIb "hotspot" mutations.
Conclusions: DICER1 is a driver of paediatric thyroid nodules and DICER1-mutated PTC may represent a distinct class of low-risk malignancies. Given the prevalence of variants in children, we advocate for inclusion of DICER1 sequencing and gene dosage determination in molecular analysis of paediatric thyroid specimens.

PMID: 29474644 [PubMed - as supplied by publisher]

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