VUMC Micro Array Core Facility, AMC, Amsterdam
Chromosomal gains and losses are thought to play a crucial role in tumorigenesis by altering the expression of genes mapping within the regions of copy number aberration. In some cases amplification, focal high level copy number increases, occur that may result in increased expression of oncogenes. However, oncogene expression may also be up-regulated by other mechanisms. In order to studied the relation between expression and amplification of several oncogenes frequently amplified and overexpressed in breast cancer. We applied microarray-based comparative genomic hybridization (array CGH) to measure and map DNA copy number aberrations in 46 ductal invasive breast tumors and quantitative real time RT-PCR to measure expression levels of CMYC, CCND1, ERBB2, ZNF217, P110alpha, ARF and ESR1. The array CGH data indicate that elevated copy number of CMYC is associated with increased copy number of much of 8q, rather than focal amplification of the locus. Copy number increases on 20q including ZNF217 and CYP24 also frequently included much of the q arm. The amplicon encompassing CCND1 at 11q13 was complex with variable numbers of closely spaced copy number peaks. On the other hand, the amplicon harboring ERBB2 was narrow. Copy number levels detected by array CGH at the ERBB2 locus were highly correlated with the expression of ERBB2 mRNA (p-value = 10-15). Copy number and expression levels ZNF217 was also correlated (p-values ..10-4). Expression levels of for ESR1, ARF, P110alpha, CCND1, CMYC and CYP24 did not correlated with copy number of their respective locus.