Genetic Mutations and Associated Prognostic Significance
| Genetic mutation | Cancers displaying genetic mutation | Prognostic significance |
|---|---|---|
| BRAF | PTC (BRAF V660E), PDTC, ATC | No clear consensus on prognostic significance; linked to extrathyroidal invasion, lymph node metastasis, vascular invasion, advanced tumor stage in primary tumor, and multifocality; linked to cellular dedifferentiation; linked to loss of iodine avidity; upregulates platelet-derived growth factor; upregulates vascular endothelial growth factor |
| PTEN | Differentiated thyroid cancers, PDTC | Uncontrolled cell growth and proliferation |
| RAS | PTC, PTC-FV, FTC, PDTC, ATC | RAS mutations alone likely associated with limited aggressiveness |
| RET/PTC rearrangements | PTC (adult and pediatric), PTC-FV, FTC | Not fully established; RET/PTC1 does not correlate with clinical pathologic features; RET/PTC3 is associated greater primary tumor size, cellular variations, and more advanced stage at diagnosis |
| TERT | 90% of human cancers, differentiated thyroid cancers, PDTC, ATC | Restores telomerase complex activity (prevents apoptosis); promotes epithelial mesenchymal transition, which promotes metastasis and cellular dedifferentiation |
| Tp53 | PTC, FTC, PDTC, ATC | Extrathyroidal extension; distant metastasis; potentially promotes cellular dedifferentiation |
BRAF = B-rapidly accelerated fibrosarcoma mutation; PTEN = phosphatase and tensin homolog mutation; RAS = rat sarcoma point mutation; PTC-FV = follicular variant of papillary thyroid cancer; RET/PTC = rearrangement during transfection/papillary thyroid cancer (RET/PTC) mutation; TERT = telomerase reverse transcriptase mutation.