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[Cancer Research 60, 854-857, February 15, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Length and Loss of Heterozygosity of an Intron 1 Polymorphic Sequence of egfr Is Related to Cytogenetic Alterations and Epithelial Growth Factor Receptor Expression1

Horst Buerger, Frank Gebhardt, Hartmut Schmidt, Alf Beckmann, Kirsten Hutmacher, Ronald Simon, Ralph Lelle, Werner Boecker and Burkhard Brandt2

Gerhard-Domagk-Institute of Pathology [H. B., R. S., W. B.], Institute of Clinical Chemistry [F. G., H. S., A. B., K. H., B. B.], and Department of Gynecology [R. L.], University of Münster, 48149 Münster, Germany

Overexpression of epithelial growth factor receptor (EGFR) is correlated with a poor prognosis and reduced steroid receptor expression. Recently, it was demonstrated that the length of a CA repeat in the intron 1 of EGFR correlated with the expression of EGFR in vitro. We investigated 112 cases of cancerous and noncancerous breast tumor samples for loss of heterozygosity (LOH) in intron 1 of the egfr gene and determined the intratumoral EGFR content and genetic alterations by comparative genomic hybridization. Heterozygous tumors with short CA repeats showed elevated EGFR expression in contrast to tumors with longer CA repeats. Tumors with LOH in intron 1 of egfr revealed higher EGFR expression when the longer allele was lost compared with loss of the shorter allele. Additionally, tumors with a loss of the long allele showed more chromosomal alterations, especially a higher frequency of amplifications. We conclude that the CA repeat status in intron 1 of the egfr gene also modulates the intratumoral EGFR content in vivo. Furthermore, LOH at the CA repeat is associated with genetically advanced tumors. Therefore, allele-specific gene expression due to LOH of the CA repeat could be assumed to be an important event in invasive breast cancer development.




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Cancer Research Clinical Cancer Research
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Copyright © 2000 by the American Association for Cancer Research.