Multiple mechanisms, such as gene mutations, amplifications, and rearrangements, as well as perturbed mitogen and receptor function, are likely to contribute to glioma formation. The MET (also known as c-met proto-oncogene located at 7q31-34 has been shown to be amplified in human gliomas, and activating mutations within the tyrosine kinase domain of MET have been causally related to tumorigenesis in hereditary papillary renal cell carcinoma. To elucidate the role of MET gene in glioma formation, sporadic gliomas from 11 patients were examined for MET gene mutations and allelic duplications or deletions by polymerase chain reaction-single strand conformational polymorphism analysis and fluorescence in situ hybridization. Three of 11 sporadic gliomas showed a deletion of one copy of the MET gene, and a specific METgene missense mutation in the remaining gene copy was detected in one of those tumors. The corresponding sequence in non-tumor DNA was normal in all cases. Three of 11 sporadic gliomas showed duplication of one copy of the MET gene, but none of them contained mutations. One tumor showed METamplification without mutation. Three showed neither allelic change nor mutation. These data suggest that somatic MET gene mutation may play a role in the development of a subgroup of sporadic gliomas. However, MET mutations appear to be absent in the majority of sporadic gliomas.