Acquired rearrangement of an amplified epidermal growth factor receptor (EGFR) gene in a human glioblastoma xenograft

Helena M. Goike, A. Charlotta Asplund, E. Helena Pettersson, L. Liu, D. Sanoudou, V. Peter Collins

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Amplification of the epidermal growth factor receptor (EGFR) occurs in about 40% of human glioblastomas. In half of these cases, rearrangements of the amplified gene result in aberrant transcripts and proteins. The most frequent rearrangement affects the external domain of the receptor and results in nonbinding of ligand and constitutive activity. Less frequent rearrangements involve changes resulting in the loss of cytoplasmic amino acid sequences necessary for downregulation of the receptor following ligand binding. Here we report the development and selection for a rearranged amplified EGF receptor, which lacks cytoplasmic amino acid sequences in a human glioblastoma xenograft. An identical aberration has previously been reported in glioblastoma tissue. The patient tumor material, as well as the first passages of the xenograft showed amplification of the EGFR gene, but no evidence of gene rearrangement or an aberrant transcript. Interphase FISH data show the amplified gene on double minutes. Between passages 3 and 16, the growth rate of the xenograft almost doubled, the rearranged amplicon became dominant, as did the aberrant transcript, indicating selection under these conditions.

Original languageEnglish
Pages (from-to)697-701
Number of pages5
JournalJournal of Neuropathology and Experimental Neurology
Volume58
Issue number7
Publication statusPublished - 1 Jul 1999
Externally publishedYes

Fingerprint

erbB-1 Genes
Glioblastoma
Heterografts
Gene Rearrangement
Epidermal Growth Factor Receptor
Amino Acid Sequence
Ligands
Interphase
Down-Regulation
Growth
Genes
Neoplasms
Proteins

Keywords

  • Astrocytoma
  • Glioma
  • Nude mice
  • Progression
  • Selection

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Goike, H. M., Asplund, A. C., Pettersson, E. H., Liu, L., Sanoudou, D., & Collins, V. P. (1999). Acquired rearrangement of an amplified epidermal growth factor receptor (EGFR) gene in a human glioblastoma xenograft. Journal of Neuropathology and Experimental Neurology, 58(7), 697-701.

Acquired rearrangement of an amplified epidermal growth factor receptor (EGFR) gene in a human glioblastoma xenograft. / Goike, Helena M.; Asplund, A. Charlotta; Pettersson, E. Helena; Liu, L.; Sanoudou, D.; Collins, V. Peter.

In: Journal of Neuropathology and Experimental Neurology, Vol. 58, No. 7, 01.07.1999, p. 697-701.

Research output: Contribution to journalArticle

Goike, HM, Asplund, AC, Pettersson, EH, Liu, L, Sanoudou, D & Collins, VP 1999, 'Acquired rearrangement of an amplified epidermal growth factor receptor (EGFR) gene in a human glioblastoma xenograft', Journal of Neuropathology and Experimental Neurology, vol. 58, no. 7, pp. 697-701.
Goike, Helena M. ; Asplund, A. Charlotta ; Pettersson, E. Helena ; Liu, L. ; Sanoudou, D. ; Collins, V. Peter. / Acquired rearrangement of an amplified epidermal growth factor receptor (EGFR) gene in a human glioblastoma xenograft. In: Journal of Neuropathology and Experimental Neurology. 1999 ; Vol. 58, No. 7. pp. 697-701.
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