PMID- 1557402 OWN - NLM STAT- MEDLINE DCOM- 19920506 LR - 20220223 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 89 IP - 7 DP - 1992 Apr 1 TI - Structural alterations of the epidermal growth factor receptor gene in human gliomas. PG - 2965-9 AB - The epidermal growth factor receptor (EGFR) gene is amplified in 40% of 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 rearrangement 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 protein from this tumor was remarkably similar to that described for several viral erbB oncogenes. Four other tumors were noted to have internal deletions of the EGFR gene. These rearrangements brought about in-frame deletions affecting either of two cysteine-rich domains in the extracytoplasmic portion of the molecule. The clonal nature of these alterations, and the fact that identical alterations were seen in more than one tumor, suggests a role for these mutant receptor proteins in tumorigenesis. Further, these studies document the existence of tumor-specific cell surface molecules resulting from somatic mutation. FAU - Wong, A J AU - Wong AJ AD - Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231. FAU - Ruppert, J M AU - Ruppert JM FAU - Bigner, S H AU - Bigner SH FAU - Grzeschik, C H AU - Grzeschik CH FAU - Humphrey, P A AU - Humphrey PA FAU - Bigner, D S AU - Bigner DS FAU - Vogelstein, B AU - Vogelstein B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Oligodeoxyribonucleotides) RN - 0 (RNA, Messenger) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Amino Acid Sequence MH - Base Sequence MH - Chromosome Deletion MH - Cloning, Molecular MH - ErbB Receptors/*genetics MH - Gene Expression MH - Gene Rearrangement MH - *Genes, Neoplasm MH - Glioma/*genetics MH - Humans MH - Molecular Sequence Data MH - Oligodeoxyribonucleotides/chemistry MH - RNA, Messenger/genetics MH - Restriction Mapping PMC - PMC48784 EDAT- 1992/04/01 00:00 MHDA- 1992/04/01 00:01 PMCR- 1992/10/01 CRDT- 1992/04/01 00:00 PHST- 1992/04/01 00:00 [pubmed] PHST- 1992/04/01 00:01 [medline] PHST- 1992/04/01 00:00 [entrez] PHST- 1992/10/01 00:00 [pmc-release] AID - 10.1073/pnas.89.7.2965 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2965-9. doi: 10.1073/pnas.89.7.2965.