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
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.