1. ¹Radiation Oncology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland
2. ²Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland
3. ³Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
4. ⁴Department of Internal Medicine, St. Vincent's Hospital The Catholic University of Korea, Seoul, Korea

Correspondence: Zhengping Zhuang, M.D., Ph.D., Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Building 10, Room 5D37 9000, Rockville Pike, Bethesda, MD 20892. e-mail: zpzhuang@helix.nih.gov; fax: 301-402-0536

Accepted 22 March 2000.

Abstract

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 polyermase 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 MET gene 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 MET amplification 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.