3' END STRUCTURE AND REARRANGEMENTS OF EGFR IN GLIOBLASTOMAS

Rearrangements of EGFR are known to occur in a significant fraction of glioblastomas, the most common and malignant form of central nervous system tumor. Although the consequences of these alterations have been described at the mRNA and protein level, little is known about human EGFR genomic sequence or organization at the rearrangement sites, To i nvestigate one group of alterations in glioblastoma, we used long-rang e PCR to synthesize a segment of the gene near its 3' end, which is fr equently rearranged in tumors with EGFR amplification. The sequence of this PCR product provided a precise map for the five 3'-terminal exon s of EGFR, designated as exons 22-26. Ten tumors were identified with rearrangements in this part of the gene, most of which resulted in the loss of 325 coding bases that constitute exons 23-25. No two tumors s hared identical donor or acceptor rearrangement sites, and the examina tion of sequences at these sites failed to support homologous recombin ation as a mechanism responsible for any of the rearrangements. Howeve r, examination of the entire exon 22-26 region for sequence motifs ass ociated with genomic instability identified two large, CA-rich tracts in intron 25. Genes Chromosomes Cancer 23:248-254, 1998. (C) 1998 Wile y-Liss, Inc.