Frequency of RET proto-oncogene mutations in patients with normal and with moderately elevated pentagastrin-stimulated serum concentrations of calcitonin

Abstract

The possibility of germline mutations of the RET proto-oncogene (exons 10, 11, 13, 14, and 16) was investigated in 75 patients (57 men, 18 women) with a negative family history for medullary thyroid carcinoma (MTC), elevated (> 10 pg/mL) basal serum concentrations of human calcitonin (hCT) and a pentagastrin (PG)-stimulated serum hCT ranging from 50-100 pg/mL. Seventy patients (50 men, 20 women) with basal serum calcitonin concentrations in the normal range served as controls. Among the 75 patients with elevated basal serum hCT concentrations we identified 1 man with the mutation S649L and 2 patients (1 man and 1 woman) with the mutation Y791F. Among the 70 individuals with normal basal calcitonin 1 man and 1 woman presented with the mutation Y791F. No other mutations (such as those in codons 618 or 634, considered to be of greater clinical relevance) were identified in either group. On the other hand, the RET proto-oncogene mutation Y791F, characterized by a low penetrance, occurs comparatively frequently among patients with normal serum calcitonin concentrations. To preselect patients for RET screening by moderately (50-100 pg/mL) pentagastrin stimulation hCT concentrations does not increase the number of identified cases of familial MTC.