Comparative genomic sequence analysis and isolation of human and mouse alternative EGFR transcripts encoding truncated receptor isoforms

This study presents the annotated genomic sequence and exon-intron organiza tion of the human and mouse epidermal growth factor receptor (EGFR) genes l ocated on chromosomes 7p11.2 and 11, respectively. We report that the EGFR gene spans nearly 200 kb and that the full-length 170-kDa EGFR is encoded b y 28 exons. In addition, we have identified two human and two mouse alterna tive EGFR transcripts of 2.4-3.0 kb using both computational and experiment al methods. The human 3.0-kb and mouse 2.8-kb EGFR mRNAs are predominantly expressed in placenta and liver, respectively, and both transcripts encode 110-kDa truncated receptor isoforms containing only the exacellular ligand- binding domain. We also have demonstrated that the aberrant 2.8-kb EGFR tra nscript produced by the human A431 carcinoma cell line is generated by spli cing to a recombinant 3'-terminal exon located in EGFR intron 16, which app arently was formed as a result of a chromosomal translocation. Finally, we have shown that the human, mouse, rat, and chicken 1.8- to 3.0-kb alternati ve EGFR transcripts are generated by distinct splicing mechanisms and that each of these mRNAs contains unique 3' sequences that are not evolutionaril y conserved. The presence of truncated receptor isoforms in diverse species suggests that these proteins may have important functional roles in regula ting EGFR activity, (C) 2000 Academic Press.