title: Mutational Analysis in Pediatric Thyroid Cancer and Correlations with Age, Ethnicity, and Clinical Presentation.
abstract: BACKGROUND
  Well-differentiated thyroid cancer (WDTC) incidence in pediatrics is rising, most being papillary thyroid carcinoma (PTC). The objective of the study was to assess the prevalence of different mutations in pediatric WDTC and correlate the genotype with the clinical phenotype.
  
  
  METHODS
  This is a single-center retrospective study. Thyroid tissue blocks from 42 consecutive pediatric WDTC patients who underwent thyroidectomy between 2001 and 2013 were analyzed at Quest Diagnostics for BRAF(V600E), RAS mutations (N,K,H), and RET/PTC and PAX8/PPARγ rearrangements, using validated molecular methods. Thyroid carcinomas included PTC, follicular thyroid carcinoma (FTC), and follicular variant of PTC (FVPTC).
  
  
  RESULTS
  Thirty-nine samples (29 females) were genotyped. The mean age at diagnosis was 14.7 years (range 7.9-18.4 years), and most were Hispanic (56.4%) or Caucasian (35.9%). The mean follow-up period was 2.9 years. Mutations were noted in 21/39 (53.8%), with both BRAF(V600E) (n = 9), and RET/PTC (n = 6) detected only in PTC. Mutations were detected in 2/5 FTC (PAX8/PPARγ and NRAS) and 3/6 FVPTC cases (PAX8/PPARγ). Of 28 PTC patients, 57.1% had mutations: 32.1% with BRAF(V600E), 21.4% with RET/PTC, and 3.6% with NRAS. Of patients with BRAF(V600E), 77.8% were Hispanic and 88.9% were >15 years, while all RET/PTC-positive patients were ≤15 years (p = 0.003). Tumor size, lymph node involvement, and distant metastasis at diagnosis (or soon after (131)I ablation) did not vary significantly based on the mutation.
  
  
  CONCLUSIONS
  BRAF(V600E) was the most common mutation, especially in older and Hispanic adolescents. A larger, ethnically diverse pediatric cohort followed long term will enable the genotypic variability, clinical presentation, and response to therapy to be better assessed.
authors.affiliation: 1 Division of Pediatric Endocrinology, San Diego, and Rady Children's Hospital San Diego , California.
authors.forename: Maria Eleni
authors.initials: ME
authors.lastname: Nikita
authors.affiliation: 2 Division of Pediatric Otolaryngology, San Diego, and Rady Children's Hospital San Diego , California.
authors.forename: Wen
authors.initials: W
authors.lastname: Jiang
authors.affiliation: 3 Hematology and Oncology, Quest Diagnostics Nichols Institute , San Juan Capistrano, California.
authors.forename: Shih-Min
authors.initials: SM
authors.lastname: Cheng
authors.affiliation: 3 Hematology and Oncology, Quest Diagnostics Nichols Institute , San Juan Capistrano, California.
authors.forename: Feras M
authors.initials: FM
authors.lastname: Hantash
authors.affiliation: 3 Hematology and Oncology, Quest Diagnostics Nichols Institute , San Juan Capistrano, California.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McPhaul
authors.affiliation: 4 Department of Pathology; University of California, San Diego, and Rady Children's Hospital San Diego , California.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Newbury
authors.affiliation: 1 Division of Pediatric Endocrinology, San Diego, and Rady Children's Hospital San Diego , California.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Phillips
authors.affiliation: 3 Hematology and Oncology, Quest Diagnostics Nichols Institute , San Juan Capistrano, California.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Reitz
authors.affiliation: 3 Hematology and Oncology, Quest Diagnostics Nichols Institute , San Juan Capistrano, California.
authors.forename: Frederic M
authors.initials: FM
authors.lastname: Waldman
authors.affiliation: 1 Division of Pediatric Endocrinology, San Diego, and Rady Children's Hospital San Diego , California.
authors.forename: Ron S
authors.initials: RS
authors.lastname: Newfield
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000208:ethnology / Q000235:genetics*; D000293:Adolescent; D000367:Age Factors; D018265:Carcinoma, Papillary, Follicular / Q000208:ethnology / Q000235:genetics*; D002454:Cell Differentiation; D002648:Child; D004252:DNA Mutational Analysis; D005006:Ethnicity; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D010641:Phenotype; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000208:ethnology / Q000235:genetics*; D055815:Young Adult