Missense mutation of the MET gene detected in human glioma

Multiple mechanisms, such as gene mutations, amplifications, and rearrangem ents, as well as perturbed mitogen and receptor function, are likely to con tribute to glioma formation. The MET (also known as c-met) proto-oncogene l ocated at 7q31-34 has been shown to be amplified in human gliomas, and acti vating mutations within the tyrosine kinase domain of MET have been causall y related to tumorigenesis in hereditary papillary renal cell carcinoma To elucidate the role of MET gene in glioma formation, sporadic gliomas from 1 1 patients were examined for MET gene mutations and allelic duplications or deletions by polyermase chain reaction-single strand conformational polymo rphism analysis and fluorescence in situ hybridization, Three of 11 sporadi c gliomas showed a deletion of one copy of the MET gene, and a specific MET gene missense mutation in the remaining gene copy was detected in one of t hose 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 M ET gene, but none of them contained mutations. One tumor showed MET amplifi cation without mutation. Three showed neither allelic change nor mutation. These data suggest that somatic MET gene mutation may play a role in the de velopment of a subgroup of sporadic gliomas, However, MET mutations appear to be absent in the majority of sporadic gliomas.