STRUCTURAL ALTERATIONS OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR GENE IN HUMAN GLIOMAS

Citation
Aj. Wong et al., STRUCTURAL ALTERATIONS OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR GENE IN HUMAN GLIOMAS, Proceedings of the National Academy of Sciences of the United Statesof America, 89(7), 1992, pp. 2965-2969
Citations number
29
ISSN journal
00278424
Volume
89
Issue
7
Year of publication
1992
Pages
2965 - 2969
Database
ISI
SICI code
0027-8424(1992)89:7<2965:SAOTEG>2.0.ZU;2-K
Abstract
The epidermal growth factor receptor (EGFR) gene is amplified in 40% o f malignant gliomas, and the amplified genes are frequently rearranged . We have characterized the genetic alterations associated with these rearrangements in five malignant gliomas. In one tumor the rearrangeme nt resulted in the deletion of most of the extracytoplasmic domain of the receptor, resulting in a hybrid mRNA between new sequences and the truncated EGFR sequence. The predicted amino acid sequence of the pro tein from this tumor was remarkably similar to that described for seve ral viral erbB oncogenes. Four other tumors were noted to have interna l deletions of the EGFR gene. These rearrangements brought about in-fr ame deletions affecting either of two cysteine-rich domains in the ext racytoplasmic portion of the molecule. The clonal nature of these alte rations, and the fact that identical alterations were seen in more tha n one tumor, suggests a role for these mutant receptor proteins in tum origenesis. Further, these studies document the existence of tumor-spe cific cell surface molecules resulting from somatic mutation.