FREQUENT RET PROTOONCOGENE MUTATIONS IN MULTIPLE ENDOCRINE NEOPLASIA TYPE 2A

The occurrence of mutations in the RET protooncogene has been investig ated in 12 multiple endocrine neoplasia type 2A families and 18 cases of sporadic thyroid medullary carcinomas and pheochromocytomas. Ten of 12 families showed single base substitutions in the RET protooncogene exons 10 and 11, coding for the extracellular domain of the protein. Tumor tissues from 2 multiple endocrine neoplasia type 2A patients wer e analyzed at the DNA and ribonucleic acid levels and revealed the sam e heterozygous mutations found in the peripheral blood lymphocytes. Th is demonstrates that both the normal and mutant alleles are expressed. No mutations in these exons were detected in the 18 cases of sporadic tumors investigated. These data provide further evidence that the mut ated RET protooncogene acts in a dominant fashion and is responsible f or the pathogenesis of this syndrome.