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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1990 Aug;81(8):773–779. doi: 10.1111/j.1349-7006.1990.tb02644.x

A Deletion Mutation within the Ligand Binding Domain Is Responsible for Activation of Epidermal Growth Factor Receptor Gene in Human Brain Tumors

Hitoshi Yamazaki 1,2, Yoshito Ohba 1,3, Norikazu Tamaoki 2, Masabumi Shibuya 1,✉
PMCID: PMC5918101  PMID: 2168866

Abstract

Two transplantable cell lines of human glioblastoma multiforme GL‐3 and GL‐5 carried an amplification and overexpression of structurally altered epidermal growth factor (EGF) receptor gene: the 140 kilodalton EGF receptors in these cases exhibited a constitutively expressed tyrosine kinase activity without the ligand. Here, we isolated the abnormal EGF receptor cDNA from GL‐5 cell line, and demonstrated that this cDNA bears a single large intramolecular deletion mutation 801 base pairs long within the ligand binding domain of EGF receptor. In other regions no amino acid substitution was observed. At the level of genomic DNA, this deletion appeared to start from the 1st intron and terminate in the 6th intron of the EGF receptor gene. However, in the two lines of glioblastoma, GL‐3 and GL‐5, the positions of the start or the end of the deletion mutation in these introns were not identical, suggesting an involvement of a unique recombination mechanism in the formation of deletion mutation. A weak but ligand‐independent transforming activity was observed in the deletion‐carrying EGF receptor cDNA.

Keywords: Oncogene, Epidermal growth factor receptor, Deletion mutation, Glioblastoma multiforme

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