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Updated: Jul 2, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Clinically Relevant Germline Variants in Children With Nonmedullary Thyroid Cancer
Karin van der Tuin1, Dina Ruano2, Jeroen Knijnenburg1
1Department of Clinical Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Context:
The underlying genetic cause of nonmedullary thyroid cancer (NMTC) in children is often unknown, hampering both predictive testing of family members and preventive clinical management.
Objective:
Our objectives were to investigated the potential heritability in the largest childhood NMTC cohort that has been genotyped to date.
Methods:
Nationwide retrospective cohort study in tertiary referral centers. In total, 97 patients diagnosed with pediatric NMTC between 1970 and 2020 were included in this study. Patients underwent germline whole genome sequencing. The main outcome measures were mutation detection yield in (1) clinically relevant tumor predisposition genes and (2) genes previously associated with NMTC.
Results:
In total, 13 of 97 patients (13%) carried a germline (likely) pathogenic variant in a well-known tumor predisposition gene: APC (n = 1), BRCA2 (n = 2), CHEK2 (n = 4), DICER1 (n = 4), HOXB13 (n = 1), and MITF (n = 1). In addition, 1 patient was diagnosed with Pendred syndrome (SLC26A4) and 9 variants of high interest were found in other NMTC candidate susceptibility genes.
Conclusion:
The reported prevalence (13%) of germline variants in well-known tumor predisposing genes and the added value of a revised personal/family history and histology led us to recommend genetic counseling for all patients with childhood NMTC. The detected tumor predisposition syndromes are associated with a risk for second cancers which necessitates additional surveillance of the index patients and presymptomatic genetic testing of at risk family members.
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