Analysis of genomic rearrangements associated with EGFRvIII expression suggests involvement of Alu repeat elements

Lori Frederick, Greg Eley, Xiao Yang Wang, C. David James*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

We have developed a polymerase chain reaction (PCR)-based strategy for the synthesis and analysis of rearranged epidermal growth factor receptor (EGFR) fragments associated with the vIII mutant receptor expressed in glioblastomas with EGFR amplification. The sequencing of aberrant tumor fragments showed that intragenic deletion rearrangements consistently involve an approximately 600-bp region in intron 7 of EGFR and several rearrangement sites interspersed throughout the large (>100 kb) first intron of this gene. Examination of the intron 7 breakpoint region revealed an Alu repeat element, and all intron 7 rearrangement sites were located within or downstream of this repeat sequence. Analysis of intron 1 for similar sequences resulted in the identification of 11 sites containing >80% homology with parts of the Alu element in intron 7. Reverse transcriptase-PCR and/or Western analysis of the tumors showed the presence of EGFRvIII cDNAs and/or proteins, respectively, in all cases for which a rearranged genomic fragment was generated by long-range PCR. Collectively, these data suggest that EGFR rearrangements, associated with the synthesis of the most common EGFR mutant, are mediated by a specific sequence element.

Original languageEnglish (US)
Pages (from-to)159-163
Number of pages5
JournalNeuro-oncology
Volume2
Issue number3
DOIs
StatePublished - Jul 2000

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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