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. 2024 Nov 18;109(12):e2214-e2221.
doi: 10.1210/clinem/dgae107.

Clinically Relevant Germline Variants in Children With Nonmedullary Thyroid Cancer

Karin van der Tuin  1 , Dina Ruano  2 , Jeroen Knijnenburg  1 , Rob B van der Luijt  1 , Hans Morreau  2 , Thera P Links  3 , Frederik J Hes  1   4 ; Dutch Pediatric Thyroid Cancer Consortium
Collaborators, Affiliations

Clinically Relevant Germline Variants in Children With Nonmedullary Thyroid Cancer

Karin van der Tuin et al. J Clin Endocrinol Metab. .

Abstract

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.

Keywords: genetics; heritability; nonmedullary thyroid cancer; pediatrics.

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References

    1. Shapiro NL, Bhattacharyya N. Population-based outcomes for pediatric thyroid carcinoma. Laryngoscope. 2005;115(2):337‐340. - PubMed
    1. Klein Hesselink MS, Nies M, Bocca G, et al. . Pediatric differentiated thyroid carcinoma in The Netherlands: a nationwide follow-up study. J Clin Endocrinol Metab. 2016;101(5):2031‐2039. - PubMed
    1. Vaccarella S, Lortet-Tieulent J, Colombet M, et al. . Global patterns and trends in incidence and mortality of thyroid cancer in children and adolescents: a population-based study. Lancet Diabetes Endocrinol. 2021;9(3):144‐152. - PubMed
    1. Goldgar DE, Easton DF, Cannon-Albright LA, Skolnick MH. Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst. 1994;86(21):1600‐1608. - PubMed
    1. Endo M, Liu JB, Dougan M, Lee JS. Incidence of second malignancy in patients with papillary thyroid cancer from surveillance, epidemiology, and End results 13 dataset. J Thyroid Res. 2018;2018:8765369. - PMC - PubMed