title: Whole-Exome Sequencing Study of Thyrotropin-Secreting Pituitary Adenomas.
abstract: Thyrotropin (TSH)-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism, and the genetic aberrations responsible remain unknown.
  
  
  
  To identify somatic genetic abnormalities in TSHomas.
  
  
  
  A single-nucleotide polymorphism (SNP) array analysis was performed on 8 TSHomas. Four tumors with no allelic losses or limited loss of heterozygosity were selected, and whole-exome sequencing was performed, including their corresponding blood samples. Somatic variants were confirmed by Sanger sequencing. A set of 8 tumors was also assessed to validate candidate genes.
  
  
  
  Twelve patients with sporadic TSHomas were examined.
  
  
  
  The overall performance of whole-exome sequencing was good, with an average coverage of each base in the targeted region of 97.6%. Six DNA variants were confirmed as candidate driver mutations, with an average of 1.5 somatic mutations per tumor. No mutations were recurrent. Two of these mutations were found in genes with an established role in malignant tumorigenesis (SMOX and SYTL3), and 4 had unknown roles (ZSCAN23, ASTN2, R3HDM2, and CWH43). Similarly, an SNP array analysis revealed frequent chromosomal regions of copy number gains, including recurrent gains at loci harboring 4 of these 6 genes.
  
  
  
  Several candidate somatic mutations and changes in copy numbers for TSHomas were identified. The results showed no recurrence of mutations in the tumors studied but a low number of mutations, thereby highlighting their benign nature. Further studies on a larger cohort of TSHomas, along with the use of epigenetic and transcriptomic approaches, may reveal the underlying genetic lesions.
authors.affiliation: Department of Medicine and Molecular Science and.
authors.forename: Santosh
authors.initials: S
authors.lastname: Sapkota
authors.affiliation: Department of Medicine and Molecular Science and.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Horiguchi
authors.affiliation: Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan; and.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tosaka
authors.affiliation: Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Tokyo 105-8470, Japan.
authors.forename: Syozo
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Medicine and Molecular Science and.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000236:Adenoma / Q000097:blood* / Q000235:genetics* / Q000601:surgery; D000328:Adult; D056915:DNA Copy Number Variations; D059472:Exome; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000097:blood* / Q000235:genetics* / Q000601:surgery; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D013972:Thyrotropin / Q000097:blood*; D055815:Young Adult
chemical_list: D013972:Thyrotropin