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Targeted Next-Generation Sequencing Analysis of a Pendred Syndrome-Associated Thyroid Carcinoma

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Abstract

Pendred syndrome is an autosomal recessive disorder characterized by hearing loss and goiter and is caused by bi-allelic mutations (homozygous or compound heterozygous) of the PDS (SLC26A4) gene. The incidence of Pendred syndrome is 7.5–10/100,000 in the general population, and it carries a 1 % risk of developing thyroid carcinoma. Herein, we report a case of a patient with Pendred syndrome who developed a follicular variant of papillary thyroid carcinoma (FVPTC)—that is approximately at an odd of 1/1,000,000. Targeted next-generation sequencing with ThyroSeq v2 was performed on the tumor, and only a TP53 mutation (TP53 p.R175H) was identified. The mutation was limited to the tumor nodule of FVPTC as shown by immunohistochemistry. This report represents the first extensive molecular study of a Pendred syndrome-associated thyroid carcinoma. The evidences support that thyroid carcinomas arising from dyshormonogenetic goiter require additional genetic alteration in addition to the purported thyroid-stimulating hormone (TSH) overstimulation. It is intrigue to note that the mutant p53 is involved in the development of a low-grade malignant thyroid tumor as FVPTC in this patient.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, and Center for Thyroid and Parathyroid disease, Staten Island University Hospital, 475 Seaview Avenue, New York, NY, 10305, USA

    Guo-Xia Tong, Qing Chang, John Carew & Richard S. Hoffman

  2. Department of Pathology and Cell Biology, Columbia University Medical Center, 630 West 168th Street, New York, NY, 10032, USA

    Diane Hamele-Bena

  3. Department of Pathology, University of Pittsburgh Medical Center, 3477 Euler Way, Pittsburgh, PA, 15213, USA

    Marina N. Nikiforova & Yuri E. Nikiforov

Authors
  1. Guo-Xia Tong
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  2. Qing Chang
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  3. Diane Hamele-Bena
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  4. John Carew
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  5. Richard S. Hoffman
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  6. Marina N. Nikiforova
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  7. Yuri E. Nikiforov
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Correspondence to Guo-Xia Tong.

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Tong, GX., Chang, Q., Hamele-Bena, D. et al. Targeted Next-Generation Sequencing Analysis of a Pendred Syndrome-Associated Thyroid Carcinoma. Endocr Pathol 27, 70–75 (2016). https://doi.org/10.1007/s12022-015-9413-4

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  • DOI: https://doi.org/10.1007/s12022-015-9413-4

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