Table 1 Mutations in thyroid cancers

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]