title: Targeted Next-Generation Sequencing Analysis of a Pendred Syndrome-Associated Thyroid Carcinoma.
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.
authors.affiliation: 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. tongguoxia@gmail.com.
authors.forename: Guo-Xia
authors.initials: GX
authors.lastname: Tong
authors.affiliation: 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.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, 630 West 168th Street, New York, NY, 10032, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Hamele-Bena
authors.affiliation: 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.
authors.forename: John
authors.initials: J
authors.lastname: Carew
authors.affiliation: 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.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Hoffman
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, 3477 Euler Way, Pittsburgh, PA, 15213, USA.
authors.forename: Marina N
authors.initials: MN
authors.lastname: Nikiforova
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, 3477 Euler Way, Pittsburgh, PA, 15213, USA.
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Nikiforov
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000150:complications* / Q000235:genetics*; D002291:Carcinoma, Papillary; D004252:DNA Mutational Analysis; D005260:Female; D016158:Genes, p53; D006044:Goiter, Nodular / Q000150:complications*; D006319:Hearing Loss, Sensorineural / Q000150:complications*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000150:complications* / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Pendred syndrome; TP53; Thyroid carcinoma