Importance of gene amplification in breast cancer

Recent studies using combination of cDNA array based expression profiling and comparative genomic hybridization have elucidated the role of gene amplification in the transcriptional program of breast cancer. In the study by Pollack et al. (2), copy number alteration and expression levels across 6691 mapped human genes were examined in 44 locally advanced breast cancer and 10 breast cancer cell lines. The data from this study suggest that at least 12% of all the variation in gene expression among the breast cancer is directly attributable to underlying variation in gene copy numbers. The total number of genomic alterations (gains and losses) correlated significantly with high grade (p = 0.008), negative estrogen receptor (ER) (p = 0.04), andp53 mutation (p = 0.0006). Of 117 high-level amplifications (representing 91 different genes), 62% (representing 54 genes) were found to be associated with at least moderately elevated mRNA levels, and 42% (representing 36 different genes) with highly elevated mRNA levels. In a similar effort, Hyman et al. examined the correlation between copy number changes and expression levels in 14 breast cancer cell lines using a cDNA microarray of 13,824 genes (3). They found 44% of highly amplified genes resulting in overexpression and 10.5% of overexpressed genes being amplified.

Together these results suggest a profound role of gene amplification in transcriptional control of gene expression in breast cancer and provide a rationale for pursuing amplified genes as a preferred target for developing therapeutics and diagnostics.

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