Distinct Amplification of an Untranslated Regulatory Sequence in the egfr Gene Contributes to Early Steps in Breast Cancer Development

摘要: Overexpression of the epidermal growth factor receptor ( egfr ) gene is a common feature in breast cancer. We demonstrated recently that expression EGFR cancer strongly correlates with length CA simple sequence repeat within first 2000 bases intron 1 [CA (CA-SSR) I; H. Buerger et al. , Cancer Res., 60: 854–857, 2000]. Using standardized semiautomated method microsatellite analysis for loss heterozygosity detection, we identified an allelic imbalance (AI) at locus 55 163 primary cases. Fine mapping chromosomal region 7p12–15 around using 10 CA-SSR markers showed mutations are frequently restricted to . Thereby, I was affected 84% patients AI. Reverse transcription-PCR 23 tissues AI excluded presence in-frame deletions between exon 2 and 7. For additional characterization underlying phenomenon leading detection analysis, quantitative 5′-nuclease assay established. In cases amplifications this shown. Kaplan-Meier revealed statistically significant worse prognosis tissue compared without Interestingly, 75% bearing tumor also normal, nontumorous tissue. Our data support assumption distinct intronic sequences gene, which enhance basic transcription activity represent one steps carcinogenesis. Furthermore, they point prognosis-associated already morphological normal