STRUCTURAL ALTERATIONS OF THE EGF RECEPTOR GENE IN HUMAN GLIOMAS

摘要

The epidermal growth factor receptor (EGFR) gene is amplified in 40% ofmalignant gliomas and the amplified genes arefrequently rearranged. The genetic alterations associated with theserearrangements are characterized in five malignant gliomas.In one tumor, the rearrangement resulted in the deletion of most of theextracytoplasmic domain of the receptor, resulting in ahybrid mRNA between new sequences and the truncated EGFR. The predicted aminoacid sequence of the protein from thistumor was remarkably similar to that described for several viral erb-Boncogenes. Four other tumors were noted to have internaldeletions of the EGF receptor gene. These rearrangements brought about in-frame deletions affecting either of two cysteine-richdomains in the extracytoplasmic portion of the molecule. The clonal nature ofthese alterations, and the fact that identicalalterations were seen in more than one tumor, suggests a role for these mutantreceptor proteins in tumorigenesis. Furthermore, thesestudies document the existence of tumor specific cell molecules resulting fromsomatic mutation.