It is plausible that the loss of NT-3 expression precedes the loss of NTRK3, which would create a clonal survival advantage for those CRC cells that silence NTRK3. Our studies suggest that inactivation of NTRK3 occurs early in the polyp→cancer sequence and that it contributes to the transformation of colon epithelial cells. The gene discussed is NTRK3; the disease is colorectal carcinoma.