ABSENCE OF MEN2A-TYPE OR 2B-TYPE RET MUTATIONS IN PRIMARY NEUROBLASTOMA TUMOR-TISSUE

Specific germline mutations in the RET proto-oncogene predispose to th e 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 neur al crest origin, such as neuroblastoma, and neuroblastoma has been obs erved in RET transgenic mice. Neuroblastoma tumour cell lines transfec ted with the MEN2A RET gene exhibit spontaneous neuritic differentiati on, whereas MEN2B-type RET transfectants demonstrate altered cell adhe sion and enhanced metastatic potential. In this study, the authors exa mined genomic DNA from 26 primary neuroblastoma tumours for MEN2A and MEN2B RET mutations, using restriction-enzyme digestion of polymerase chain reaction products as an alternative to direct sequencing. Examin ation of RET exons 10 (codons 611, 618, 620), 11 (codons 632, 633, 634 ) and 16 (codon 918) in all 26 tumours revealed no RET mutations. Take n together these data suggest that abnormalities of the RET signalling pathway, rather than oncogenic, MEN2-type RET activation by mutation, may play a role in neuroblastoma tumorigenesis. (C) 1998 Academic Pre ss.