NO MUTATIONS FOUND BY RET MUTATION SCANNING IN SPORADIC AND HEREDITARY NEUROBLASTOMA

Neuroblastoma occasionally occurs in diseases associated with abnormal neurocrest differentiation, e.g. Hirschsprung disease. Expression stu dies in developing mice suggest that the proto-oncogene RET plays a ro le in neurocrest differentiation. In humans expression of RT is limite d to certain tumor types, including neuroblastoma, that derive from mi grating neural crest cells. Mutations of RET are found associated with Hirschsprung disease. These data prompted us to investigate expressio n of RET and to search for gene mutations in neuroblastoma. Out of 16 neuroblastoma cell lines analyzed, 9 show clear expression of RET in a Northern blot analysis. In a single-strand conformation polymorphism (SSCP) analysis of all exons, no mutations were detected other than ne utral polymorphisms. In a patient with neuroblastoma, from a family in which different neurocrestopathies, including neuroblastoma and Hirsc hsprung disease, had occurred, we also failed to detect RET mutations. Possibly, expression of RET in neuroblastoma merely reflects the diff erentiation status of the tumor cells. The absence of mutations sugges ts that RET does not play a crucial role in the tumorigenesis of neuro blastoma.