Sugawa N, Ekstrand A J, James C D, Collins V P
Ludwig Institute for Cancer Research, Clinical Group, Stockholm, Sweden.
Proc Natl Acad Sci U S A. 1990 Nov;87(21):8602-6. 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.
在人体胶质母细胞瘤中，已发现表皮生长因子受体基因在体内存在扩增和重排现象。在此，我们展示了来自六个原发性人类胶质母细胞瘤中相应且独特重排基因的异常表皮生长因子受体转录本剪接位点的序列，这些基因与未重排的表皮生长因子受体基因共同扩增且共同表达。这六个肿瘤中的每一个都包含由于扩增基因的缺失重排而导致的从外显子1到外显子8相同剪接产生的异常转录本，其缺失程度在这些肿瘤中各不相同。尽管存在肿瘤间的这种变异性，但每个基因内重排都会导致相同的801个编码碱基（外显子2至7）缺失，并在其相应转录本的新剪接位点产生一个新密码子。然而，这些重排并不影响信号肽的mRNA序列、前五个密码子或重排下游的阅读框。
