期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 106, 期 4, 页码 968-977出版社
ENDOCRINE SOC
DOI: 10.1210/clinem/dgab025
关键词
DICER1 mutation; thyroid nodules; thyroid cancer genes
资金
- Canadian Institutes of Health Research [FDN-148390]
- la Caixa Foundation [LCF/BQ/PI19/11690009, ID100010434]
- Fundacion Mutua Madrilena
This study found that DICER1 hotspot mutations are present in adult thyroid nodules and appear to be mutually exclusive with alterations in other thyroid cancer-related genes. DICER1 hotspot mutations often accompany a second pathogenic variant, suggesting the presence of occult DICER1 syndrome in adults with thyroid nodules.
Context: DICER1 mutations are found in multinodular goiter and differentiated thyroid carcinoma in children, and can be a manifestation of DICER1 syndrome, but the prevalence of DICER1 mutations and their significance in adult-onset thyroid nodules is unknown. Objective: Determine (1) the prevalence of DICER1 hotspot mutations in thyroid nodules; (2) the frequency of a second DICER1 pathogenic variant in thyroid nodules with DICER1 hotspot mutations; (3) the prevalence of other thyroid cancer driver mutations in thyroid nodules with and without DICER1 hotspot mutations. Methods: Population-based study of 14 993 consecutive fine needle aspiration biopsies of thyroid nodules evaluated by ThyroSeq v3. From 214 DICER1 hotspot-positive cases, we selected 61, matched to DICER1 hotspot-negative nodules. We performed full sequencing of all exons and exon-intron boundaries of DICER1. Setting: Commercial and university-based laboratories in the United States and Canada. Results: Among 14 993 thyroid nodules, 214 (1.4%) revealed a DICER1 hotspot mutation. A second pathogenic/likely pathogenic variant in DICER1 was found in 45/59 (76%) DICER1 hotspot-positive nodules studied while no other DICER1 variant was identified in the DICER1 hotspot-negative group by full DICER1 sequencing. Other alterations in thyroid-related genes were significantly more frequent in DICER1 hotspot-negative nodules (32/61) than in DICER1 hotspot-positive nodules (4/59) (P < .0001). Conclusion: DICER1 alterations occur in a proportion of adult thyroid nodules and appear mutually exclusive with alterations in other thyroid cancer-related genes. DICER1 hotspot mutations occur with a second hit in most cases and could suggest occult DICER1 syndrome in adults with thyroid nodules.
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