Acquired Rearrangement of an Amplified Epidermal Growth Factor Receptor (EGFR) Gene in a Human Glioblastoma Xenograft

• Published in: Journal of neuropathology and experimental neurology Vol. 58; no. 7; pp. 697 - 701
• Main Authors: Goike, Helena M, Asplund, A.Charlotta, Petersson, E Helene, Liu, L, Sanoudou, D, Collins, V Peter
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Association of Neuropathologists, Inc 01.07.1999; Lippincott Williams & Wilkins; Oxford University Press
• Subjects: Animals; Base Sequence - genetics; Biological and medical sciences; ErbB Receptors - genetics; Gene Amplification - genetics; Gene Rearrangement - genetics; Glioblastoma - genetics; Humans; In Situ Hybridization, Fluorescence; Medical sciences; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Mice, Nude; Neoplasm Transplantation; Neurology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Transplantation, Heterologous; Tumors of the nervous system. Phacomatoses; Glioblastoma; Reverse transcription; Carcinogenesis; Malignant glioma; Epidermal growth factor; Fluorescence in situ hybridization; Established cell line; Human; Nervous system diseases; Cytokine; Rodentia; Implantation; Malignant tumor; Polymerase chain reaction; Pathology; Vertebrata; Growth factor receptor; Mammalia; Mouse; Polypeptide; Animal; Central nervous system disease; Gene rearrangement; Cytogenetics; Molecular biology; Growth factor
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1097/00005072-199907000-00003

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.