Mutational activation of BRAF is not a major event in sporadic childhood papillary thyroid carcinoma

Eli Rosenbaum, Gregory Hosler, Marianna Zahurak, Yoram Cohen, David Sidransky, William H. Westra

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)898-902
Number of pages5
JournalModern Pathology
Volume18
Issue number7
DOIs
StatePublished - Jul 1 2005

Keywords

  • Childhood papillary carcinoma
  • Mitogen-activated protein kinase pathway
  • RET

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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