The RET (Rearranged during transfection) proto-oncogene was identified as a transforming DNA fragment originating by genetic rearrangement in vitro.It has subsequently been found rearranged or mutated in a number of tumors, in particular thyroid, colorectal and lung cancer. The c-ret gene encodes a member of the receptor tyrosine kinase superfamily, of which the prototypes are growth factor receptors such as the epidermal growth factor receptor (EGFR), the high affinity nerve growth factor receptor (Trk), the Steel factor receptor (Kit) and the hepatocyte growth factor receptor (Met). Each of these proteins has an extracellular ligand-binding domain, a transmembrane domain and a cytoplasmic domain that has protein tyrosine kinase activity. A significant fraction of thyroid carcinomas harbor genetic abnormalities involving RET, including chromosomal rearrangements and point mutations. Several gene fusions have been described, containing the catalytic domain of RET juxtaposed in frame with an oligomerization domain from an unrelated gene, in papillary thyroid cancer (RET/PTC), colorectal cancer and lung adenocarcinoma.

References

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