GERMLINE RET MUTATIONS IN MEN 2A AND FMTC AND THEIR DETECTION BY SIMPLE DNA DIAGNOSTIC-TESTS

Multiple endocrine neoplasia type 2A (MEN 2A) and familiar medullary t hyroid carcinoma (FMTC) are two closely related cancer syndromes inher ited in an autosomal dominant manner. Mutations in the RET proto-oncog ene were found in MEN 2A and FMTC families. In this study we report se ven different germline mutations in the RET proto-oncogene in five of five MEN 2A and five of six FMTC families. Each of the mutations invol ves a cysteine residue in the extracellular cysteine-rich domain of th e RET receptor tyrosine kinase. We developed simple polymerase chain r eaction based diagnostic tests for all seven mutations in these famili es.