Differentiated thyroid cancers (DTC), both papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC), are generally associated with an indolent disease course and, as they maintain the typical features of thyroid cells.Aberrant signalling pathways have been implicated in the onset, progression and invasiveness of DTCs. The most common genetic changes in PTC are point mutations in BRAF and RAS and rearrangement of the RET protooncogene. Several RET/PTC rearrangements have been described, almost exclusively in PTC cells, mainly in radioinduced PTC, but also in a not negligible percentage of sporadic cases. In FTC, point mutations of RAS and rearrangements of PPARg and PAX8 genes, to create the PPFP fusion gene, are the most common oncogenic alterations but, to a lesser extent, also PTEN deletion/mutation, PIK3CA and IDH1 mutations can be found. 
At variance from PTC and FTC, in which oncogene mutations are almost mutually exclusive, PDTC and even more ATC are characterised by a higher number of mutations in the same tumoural tissue and the overexpression of these proteins is probably responsible for a more aggressive phenotype. The most prevalent oncogene alterations in ATC are p53 point mutations, BRAFV600E, PIK3CA, PTEN, IDH1 and ALK mutations, whereas in PDTC, beta-catenin (CTNNB1), p53 and BRAFV600E mutations are the most frequent. Both in ATC and PDTC the prevalence of TERT promoter mutations is high and typically associated with a greater aggressiveness.

References

1.L. Valerio, L. Pieruzzi, et al. Clinical Oncology 29 (2017) 316e324.