Multiple mRNA isoforms of the human RET proto-oncogene generated by alternate splicing

The RET proto-oncogene encodes a receptor tyrosine kinase. We and others have recently shown that distinct germline mutations of the RET proto-oncogene account for the majority of cases of the dominantly inherited multiple endocrine neoplasia (MEN) type 2 syndromes, and can cause a dominantly inherited form of Hirschsprung disease, a disorder of development of the autonomic innervation of the gut. RET is also oncogenically activated in some sporadic thyroid and adrenal tumours. Here we report the characterisation of multiple mRNA isoforms of RET generated by alternate splicing. Two isoforms are predicted to encode membrane-spanning receptors with a truncated extracellular ligand-binding domain. A third isoform is predicted to encode a soluble, secreted form of the receptor. These mRNA isoforms are expressed in both normal and tumour tissues.