Identical Splicing of Aberrant Epidermal Growth Factor Receptor Transcripts from Amplified Rearranged Genes in Human Glioblastomas

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 87; no. 21; pp. 8602 - 8606
• Main Authors: Sugawa, Noriaki, Ekstrand, A. Jonas, James, C. David, Collins, V. Peter
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01-11-1990; National Acad Sciences
• Subjects: Amino Acid Sequence; Base Sequence; Blotting, Northern; Codons; Complementary DNA; DNA; DNA, Neoplasm - genetics; ErbB Receptors - genetics; Exons; Gene Rearrangement; Genes; Glioblastoma; Glioma - genetics; Humans; Introns; Molecular Sequence Data; Oligonucleotide probes; Polymerase chain reaction; Polymerase Chain Reaction - methods; RNA Splicing; Transcription, Genetic; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.21.8602

The epidermal growth factor receptor gene has been found to be amplified and rearranged in human glioblastomas in vivo. Here we present the sequence across a splice junction of aberrant epidermal growth factor receptor transcripts derived from corresponding and uniquely rearranged genes that are coamplified and coexpressed with non-rearranged epidermal growth factor receptor genes in six primary human glioblastomas. Each of these six tumors contains aberrant transcripts derived from identical splicing of exon 1 to exon 8 as a consequence of a deletion-rearrangement of the amplified gene, the extent of which is variable among these tumors. In spite of this intertumoral variability, each intragenic rearrangement results in loss of the same 801 coding bases (exons 2-7) and creation of a new codon at the novel splice site in their corresponding transcripts. These rearrangements do not, however, affect the mRNA sequence for the signal peptide, the first five codons, or the reading frame downstream of the rearrangement.