Some somatic oncogene mutations (BRAF, NRAS, HRAS, KRAS) as well as gene translocations (RET/PTC, PAX8/PPAR-gamma) have been associated with the development of thyroid cancer.
Fourteen FNMTCs in patients from seven families were analyzed in terms of involvement of the four susceptibility loci, and 63 thyroid cancer tumors [FNMTC (29) and NMTC (34)] were evaluated for the occurrence of mutations in BRAF, and H-, N-, and K-RAS, using polymerase chain reaction, single-strand conformation polymorphism (PCR-SSCP) analysis, and direct sequencing.
The effect of activating somatic mutations in the KRAS and BRAF genes on the responsiveness to sunitinib was evaluated in a panel of thyroid cancer cell lines harboring wild-type KRAS and BRAF genes, the RET/PTC1 rearrangement, the G12R KRAS, or the V600E BRAF mutation.
We conclude that wild-type K-Ras.GTP in association with Gal-3 contributes to thyroid carcinoma malignancy and that Ras inhibition might be a useful treatment strategy against these deadly tumors.