Three novel mutations in the RET proto-oncogene.

Medullary thyroid carcinoma (MTC) occurs as a sporadic tumor or in connection with inherited cancer syndromes of multiple endocrine neoplasia type 2 and familial MTC. Missense RET proto-oncogene mutations and small in-frame deletions are found in most of the cases. In a significant amount of sporadic MTC cases somatic mutation at codon 918 (exon 16), or at codons 609, 611, 618, 620 (exon 10), or codons 630, 634 (exon 11) appear. We report here on three new somatic cell missense mutations of the RET proto-oncogene associated with sporadic MTC. In one tumor mutation at codon 922 TCC(Ser)→TTC(Phe) in exon 16 was found. In another tumor two mutations at codons 639 GCA(Ala)→GGA(Gly) and 641 GCT(Ala)→CGT(Arg) in the exon 11 were observed. Allele-specific PCR followed by sequencing demonstrated the presence of both mutations at the same allele.