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Table 1 Mutations in thyroid cancers

From: Novel targeted therapies and immunotherapy for advanced thyroid cancers

Thyroid cancer type Mutation Description and significance Reference
Differentiated thyroid cancers B-RAF B-RAF point mutations (particularly glutamate substitution for valine at residue 600, V600E) are present in 30–70% of patients with PTC [96,97,98,99,100,101,102,103,104]
RAS RAS oncogene mutations are manifested in 15–20% of PTC and 40–50% of FTC [105,106,107,108,109,110,111]
RET/PTC rearrangements RET/PTC1 and RET/PTC3 together comprise > 90% of RET/PTC mutations in thyroid cancer); RET/PTC2 represents less than 5%. Combined, RET/PTC rearrangements are found in ~ 13% of PTC [112,113,114,115,116,117,118,119]
PAX8-PPARγ translocations PAX8 drives the expression of many thyroid-specific genes such as those encoding thyroglobulin, the sodium iodide symporter and thyroid peroxidase. The PAX8-PPARγ translocations are found in 35% of FTC and vascular invasion and tumor proliferation have been linked to these translocations. [120,121,122,123,124,125]
Telomerase reverse transcriptase gene (TERT) mutations Found to be overexpressed in DTC; 11% of FTC and 16–40% of PTC (frequently in association to B-RAF mutations) were found to bear TERT mutations. Coexistence of TERT with BRAF mutation was concluded to have the worst prognosis for DTC patients especially those with PTC subtype [126]. However, studies examining TERT as a therapeutic target are lacking. [126,127,128]
PIK3CA PIk3CA gene encodes for catalytic subunits in PI3K leading to activating the proliferative cascade of PI3K/AKT pathway. Increased copy numbers of this gene has been found in 24% of FTC and 42% of ATC. [25]
PTEN PTEN normally antagonizes and terminates the signaling of the PI3K/Akt pathway. It was found that around 12% of ATC exhibit mutated or deleted PTEN genes and hence over activation of the proliferative PI3k pathway and more tumoral aggressiveness. [25]
Medullary thyroid cancers RET mutations > 60% of MTC have been linked to somatic RET oncogene mutations. [129]