Concomitant BRAF(V600E) mutation and RET/PTC rearrangement is a frequent occurrence in papillary thyroid carcinoma.

BACKGROUND: The tyrosine kinase receptors/RAS/RAF/MAPK cascade is a site of mutational events associated with thyroid carcinogenesis. Some studies suggest the reciprocal exclusion of different oncogenes in the mitogen-activated protein kinase cascade, whereas others suggest that BRAF mutations and RET rearrangements can simultaneously occur in sporadic cases. The aim of this study was to determine the prevalence of concomitant BRAF(V600E) mutation and RET/PTC rearrangements in the same tumor and its association with some clinicopathological features.

METHODS: The percentage of mutant BRAF alleles and the presence of RET/PTC rearrangements were determined by means of pyrosequencing and Southern blot analysis of reverse transcription polymerase chain reaction products in a series of 72 conventional papillary thyroid carcinomas (PTCs). Then, the associations between clinicopathological characteristics and mutation status were assessed.

RESULTS: BRAF(V600E) alleles were present in 32 out of 72 PTCs (44.4%) in the range of 5.1-44.7% of total BRAF alleles. RET/PTC was present in 26 tumors (36.1%). Concomitant subclonal BRAF and RET/PTC were demonstrated in 14 PTCs (19.4%), and none of the oncogenes was detected in 22 tumors (30.5%). Only BRAF(V600E) was associated with a more advanced tumor staging.

CONCLUSIONS: The present study demonstrates that concomitant BRAF mutation and RET/PTC rearrangement is a frequent event in PTC.