Simultaneous occurrence of BRAF mutation and RET/PTC rearrangement is frequent in papillary thyroid carcinoma
A. Guerra1, V. Marotta2, V. Di Stasi1, A. Volpe1, A. Murino1, M. Di Stasi1 & M. Vitale1
Context: Initial studies reported that RET rearrangements, RAS mutations and BRAF mutation are mutually exclusive genetic events in papillary thyroid carcinoma (PTC). Subsequently, simultaneous occurrence of BRAF mutation and RET/PTC or H4-PTEN has been described in few PTC cases, indicating that these genetic alterations might coexist in PTC in the same cell or in different cells, at least sporadically. In light of the recent finding that frequently BRAF mutation is present only in a subset of cells in PTC, we analyzed more extensively the possibility that BRAFT1799A and RET/PTC can coexist in the same tumor.
Study design: Total RNA extracted from 75 FNABs classified as PTC at histology, were analyzed by Southern blot on RT-PCR for the presence of RET/PTC-1 and RET/PTC-3 rearrangements. Genomic DNA extracted from the same samples was analyzed by pyrosequencing for the presence of the BRAFT1799A mutation.
Results: RET rearrangements were present in 28 over 75 PTC (37.3%, 9 RET/PTC-1 and 19 RET/PTC-3). In one sample, both RET rearrangements coexisted. BRAFT1799A was present in 42 (56%) in the range 44.75.1% of total BRAF mutated alleles. In 14 samples, both a RET rearrangement and BRAF mutation were present (14.7%). In these tumors, BRAF mutation was always as a subclonal or oligoclonal occurrence in the range 37.56%.
Conclusions: These data demonstrate that RET rearrangements and BRAF mutation are not mutually exclusive but rather are frequently co-expressed in the same PTC. The data, do not exclude the hypothesis of a coexistence of the two oncogenes in different cells within the tumor.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.