RAS point mutations and PAX8/ PPARgamma (PAX8/ PPARG fusion protein, PPFP) rearrangements are the most frequent molecular events in FTC. Noteworthy, these genetic lesions are also present in FTA. The frequency of RAS mutations in FTC is about 40%, mainly in codons 12, 13, and 61. The alterations in NRAS 61 codon are related to a more aggressive FTC course. FTCs harbouring RAS mutation may demonstrate a higher risk of de differentiation. PPFP rearrangements are present in 26– 56% of FTCs, in 0– 13% of FTAs, 0– 3% of HCCs, and 0– 1% of PTCs. They result from the translocation between chromosomes 2 and 3 [t(2;3)(q13;p25)] and, although the function of both genes is known, the role of PPFP fusion protein is still unclear. It leads to the downregulation of PPARG suppressor gene and the deregulation of PAX8, which may contribute to cancer development. In addition to PPFP translocation, another PPARG rearrangement has been reported in FTC with CREB3L2 gene as a fusion partner. TERT promoter mutations are more frequent in FTC compared to PTC and concern, on average, 17% of FTC. A small number of mutations recently detected in FTC involve DICER1, IDH1, EZH1, and genes related to the PI3K- PTEN- AKT pathway.
In contrary to PTC, copy number changes are common in FTC. Losses of chromosome 3p are common alterations, however, additional loss of heterozygosity (LOH) sites were detected in FTC, including 1p, 6p/ q, 8p/ q, 9p, 11q, 13q, 18q, and 22q. Two amplifications, in turn, concerning 11p and 17q, were suggested as potential early molecular events involved in cancer initiation.
The knowledge about the miRNA profile in FTC is very limited. Increased expression of miR- 181 and miR- 200 family and downregulation of miR- 199 was reported in FTC, and two miRNAs, miRNA- 7- 5p and miR- 206, were proposed as potential markers able to distinguish FTA from FTC. Moreover, miR- 146b and miR- 221, previously reported as upregulated in PTC, showed increased expression in FTC as well, which suggests these two miRNAs are common players in both DTC types.
