title: Mutation in BRAF and Other Members of the MAPK Pathway in Papillary Thyroid Carcinoma in the Pediatric Population.
abstract: BACKGROUND
  Papillary thyroid carcinoma (PTC) is an uncommon tumor in the pediatric population. A limited number of studies have examined genetic mutations affecting the mitogen-activated protein kinase (MAPK) pathway in the pediatric population.
  
  
  OBJECTIVE
  To examine mutations affecting this pathway in PTC in our pediatric population and compare the BRAF V600E mutation rates in pediatric and adult tumors.
  
  
  METHODS
  Eighty-four patients, including 14 pediatric and 70 adult, with PTC were tested for the BRAF V600E mutation by using real-time polymerase chain reaction and sequencing. Additionally, we examined the rate of RAS point mutations with real-time polymerase chain reaction and rearrangements of RET/PTC1 and RET/PTC3 in the pediatric group with fluorescence in situ hybridization. Clinical and histologic data were compared as well.
  
  
  RESULTS
  Of 77 tumors that had an interpretable result, the BRAF V600E mutant was identified in 4 of 13 pediatric patients (31%) and 43 of 64 adult patients (67%), which was a significant difference (using Fisher exact test, P = .03). One pediatric and 6 adult cases did not reveal an interpretable result with melting curve analysis. One of these cases harbored a rare 3-base pair deletion mutation (c.1799_1801delTGA). Mutations in RAS genes were not seen in any pediatric tumors. One tumor with a RET/PTC1 rearrangement and another with RET/PTC3 were identified in the pediatric population (15%).
  
  
  CONCLUSIONS
  The rate of the BRAF V600E mutation in the pediatric population is significantly lower than that seen in the adult population. Mutations in RAS do not contribute significantly to pediatric PTC. This experience from our institution adds to the growing body of knowledge regarding tumor genetics in pediatric PTC.
authors.affiliation: From the Department of Pathology, MD Anderson Cancer Center, Houston, Texas (Dr Gertz);
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Gertz
authors.affiliation: the Division of Molecular Genomic Pathology, University of Pittsburgh, Pennsylvania (Dr Nikiforov);
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nikiforov
authors.affiliation: the Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison (Drs Lloyd and Rehrauer);
authors.forename: William
authors.initials: W
authors.lastname: Rehrauer
authors.affiliation: and the School of Public Health, Louisiana State University, New Orleans (Dr McDaniel). Dr Gertz is now located at the Department of Pathology, OhioHealth Riverside Methodist Hospital, Columbus, Ohio.
authors.forename: Lee
authors.initials: L
authors.lastname: McDaniel
authors.affiliation: the Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison (Drs Lloyd and Rehrauer);
authors.forename: Ricardo V
authors.initials: RV
authors.lastname: Lloyd
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics*; D002291:Carcinoma, Papillary; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics*; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins