Clinical and molecular aspects of multiple endocrine neoplasia

The discovery that RET proto-oncogene mutations are responsible for MEN2 and FMTC was a landmark from the perspective of many, including the geneticist involved in basic science, the molecular diagnostician, the clinician, and MEN2/FMTC families. The discovery has provided basic information concerning the role of proto-oncogenes and proto-oncogene activation. The identification of MEN2/FMTC-associated mutations has also allowed for the availability of direct mutation analysis in the routine clinical laboratory. The discovery has resulted in definitive risk assessment for members of FMTC/MEN2 kindreds and improved management of RET mutation carriers. The discovery also links two realms of genetics that are often separated: cancer genetics and 'classic' mendelian disorders. Finally, information concerning the molecular basis of Hirschsprung disease indicates that our understanding of the phenotypic consequences of RET mutations is considerable but not yet complete.