Chimeric tyrosine kinases in papillary thyroid carcinoma

Schematic representation of chimeric tyrosine kinases in papillary thyroid carcinoma. The RET and NTRK1 genes code for tyrosine kinases that are not normally expressed in thyroid epithelial cells. Gene rearrangements that elicit expression of these tyrosine kinases in thyroid epithelial cells cause papillary carcinomas; such rearrangements appear to occur more frequently following external beam radiation or exposure to radiation after a nuclear accident. When the appropriate gene rearrangement occurs, a chimeric gene is formed and the resultant chimeric protein is expressed. The new 5' end of the chimeric gene confers expression in thyroid epithelial cells and codes for the amino terminus of the chimeric protein. Expression of the active tyrosine kinases presumably activates growth pathways by a cascade beginning with tyrosine phosphorylation. The chimeric RET genes are referred to as RET/PTC and the chimeric NTRK1 genes are referred to as TRK.