Clinical and Molecular Characteristics May Alter Treatment Strategies of Thyroid Malignancies in DICER1 Syndrome

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Publication year
2019Source
Journal of Clinical Endocrinology and Metabolism, 104, 2, (2019), pp. 277-284ISSN
Publication type
Article / Letter to editor

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Organization
Human Genetics
Radboudumc Extern
Journal title
Journal of Clinical Endocrinology and Metabolism
Volume
vol. 104
Issue
iss. 2
Page start
p. 277
Page end
p. 284
Subject
Radboudumc 14: Tumours of the digestive tract RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 9: Rare cancers RIHS: Radboud Institute for Health SciencesAbstract
Context: DICER1 syndrome is a rare autosomal-dominantly inherited disorder that predisposes to a variety of cancerous and noncancerous tumors of mostly pediatric and adolescent onset, including differentiated thyroid carcinoma (DTC). DTC has been hypothesized to arise secondarily to the increased prevalence of thyroid hyperplastic nodules in syndromic patients. Objective: To determine somatic alterations in DICER1-associated DTC and to study patient outcomes. Design: Retrospective series. Setting: Tertiary referral centers. Patients: Ten patients with germline pathogenic DICER1 variants and early-onset DTC. Methods: Somatic DICER1 mutation analysis, extensive somatic DNA variant and gene fusion analyses were performed on all tumors. Results: Median age at DTC diagnosis was 13.5 years and there was no recurrent or metastatic disease (median follow-up, 8 years). All thyroid specimens showed diffuse nodular hyperplasia with at least one focus suspicious of DTC but without infiltrative growth, extrathyroidal extension, vascular invasion, or lymph node metastasis. Most of the individual nodules (benign and malignant) sampled from the 10 tumors harbored distinct DICER1 RNase IIIb hotspot mutations, indicating a polyclonal composition of each tumor. Furthermore, nine of 10 DICER1-related DTCs lacked well-known oncogenic driver DNA variants and gene rearrangements. Conclusion: On the basis of our clinical, histological, and molecular data, we consider that most DICER1-related DTCs form a low-risk subgroup. These tumors may arise within one of multiple benign monoclonal nodules; thus, hemi-thyroidectomy or, more likely, total thyroidectomy may often be required. However, radioiodine treatment may be unnecessary given the patients' ages and the tumors' low propensity for metastases.
This item appears in the following Collection(s)
- Academic publications [227437]
- Electronic publications [107154]
- Faculty of Medical Sciences [86157]
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