Mutational activation of BRAF is not a major event in sporadic childhood papillary thyroid carcinoma.
Papillary thyroid carcinoma may encompass a mixed group of neoplasms where divergence in clinical behavior may reflect distinct genetic alterations. For example, young patients with papillary thyroid carcinoma have a better prognosis than affected adults, and their carcinomas are much more likely to harbor chromosomal rearrangements involving the RET proto-oncogene. Mutational activation of the BRAF oncogene has recently been identified as the most common genetic alteration in papillary thyroid carcinoma, but little is known about its frequency as a function of patient age. We tested 20 papillary thyroid carcinomas from young patients ranging from 10 to 17 years of age for the thymine (T) --> adenine (A) missense mutation at nucleotide 1796 in the BRAF gene using a newly developed assay that employs a novel primer extension method (Mutector assay). The prevalence of BRAF mutation was compared with a larger group of papillary thyroid carcinomas from previously tested adult patients (>20 years). BRAF mutations were not common in papillary thyroid carcinomas from young patients compared to their counterparts in adults (20 vs 77%; OR=13.3, 95% confidence interval (CI)=3.4-56.5; P<0.0001), but they become increasingly prevalent with advancing patient age (OR as a function of age at 10-year intervals=1.80 CI=1.33-2.44; P<0.001). Unlike papillary thyroid carcinomas that arise in adults, mutational activation of BRAF is not a major genetic alteration in papillary thyroid carcinomas that arise in young patients. The increasing frequency of BRAF mutations as a function of age could help account for the well documented but poorly understood observation that age is a relevant prognostic indicator for patients with papillary thyroid carcinoma.
Rosenbaum
Eli
E
Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Hosler
Gregory
G
Zahurak
Marianna
M
Cohen
Yoram
Y
Sidransky
David
D
Westra
William H
WH
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002648:Child; D004252:DNA Mutational Analysis; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D000090063:Proto-Oncogene Mas; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf