LightCycler PCR Assay for Genotyping Codon 634 Mutations in the RET Protooncogene

Mutations of the RET protooncogene are associated with several disorders, including Hirschsprung disease, familial medullary thyroid carcinoma (FMTC), and multiple endocrine neoplasia type 2A (MEN 2A) and type 2B (MEN 2B). More than 85% of the causing mutations in MEN 2A families affect codon 634 in exon 11 of the RET protooncogene (1)(2)(3)(4)(5). Although all possible changes except the conservative TGC to TGT and the TGC to the termination codon TGA have been found in codon 634 in MEN 2A families, TGC (Cys) to TAC (Tyr) and TGC to CGC (Arg) are by far the most prevalent. Mutations in codon 634 are also responsible for 25–30% of patients with FMTC. Mutation analysis of RET permits identification of MEN 2A carriers and can reduce morbidity and mortality through early intervention (6). The methods used to detect RET mutations are time-consuming and require optimization of the PCR to avoid nonspecific PCR …