Length and loss of heterozygosity of an intron 1 polymorphic sequence of egfr is related to cytogenetic alterations and epithelial growth factor receptor expression

Overexpression of epithelial growth factor receptor (EGFR) is correlated wi th a poor prognosis and reduced steroid receptor expression. Recently, it w as demonstrated that the length of a CA repeat in the intron 1 of EGFR corr elated with the expression of EGFR in vitro. We investigated 112 cases of c ancerous and noncancerous breast tumor samples for loss of heterozygosity ( LOH) in intron 1 of the egfr gene and determined the intratumoral EGFR cont ent and genetic alterations by comparative genomic hybridization, Heterozyg ous tumors with short CA repeats showed elevated EGFR expression in contras t to tumors with longer CA repeats. Tumors with LOH in intron 1 of egfr rev ealed higher EGFR expression when the longer allele was lost compared with loss of the shorter allele, Additionally, tumors with a loss of the long al lele showed more chromosomal alterations, especially a higher frequency of amplifications. We conclude that the CA repeat status in intron 1 of the eg fr gene also modulates the intratumoral EGFR content in vivo. Furthermore, LOH at the CA repeat is associated with genetically advanced tumors. Theref ore, allele-specific gene expression due to LOH of the CA repeat could be a ssumed to be an important event in invasive breast cancer development.