Absence of MEN2A- or 2B-typeRETmutations in primary neuroblastoma tumour tissue

Abstract

Specific germline mutations in theRETproto-oncogene predispose to the familial cancer syndromes: multiple endocrine neoplasia (MEN) types 2A and 2B, and familial medullary thyroid carcinoma. Expression of the RET receptor tyrosine kinase is tightly restricted to tumours of neural crest origin, such as neuroblastoma, and neuroblastoma has been observed inRETtransgenic mice. Neuroblastoma tumour cell lines transfected with the MEN2ARETgene exhibit spontaneous neuritic differentiation, whereas MEN2B-typeRETtransfectants demonstrate altered cell adhesion and enhanced metastatic potential. In this study, the authors examined genomic DNA from 26 primary neuroblastoma tumours for MEN2A and MEN2BRETmutations, using restriction enzyme digestion of polymerase chain reaction products as an alternative to direct sequencing. Examination ofRETexons 10 (codons 611, 618, 620), 11 (codons 632, 633, 634) and 16 (codon 918) in all 26 tumours revealed noRETmutations. Taken together these data suggest that abnormalities of the RET signalling pathway, rather than oncogenic, MEN2-typeRETactivation by mutation, may play a role in neuroblastoma tumorigenesis.