CytoScan HD array data from Human mammary epithelian cells after Cyclin E overexpression

Cyclin E, a key cell cycle regulatory protein, has been linked to oncogenesis when dysregulated. We have previously shown that overexpression of cyclin E causes replication stress, leading to failure to complete replication at specific chromosomal loci during S phase of the cell cycle. This, in turn promotes chromosomal damage during anaphase. Here we show that non-transformed human mammary epithelial cell clones that survive such aberrant mitoses, have a specific and reproducible pattern of chromosomal Copy Number Alterations (CNAs) that we have characterized and termed the cyclin E CNA signature. Using a number of computational approaches, we show that this signature resembles one specific CNA pattern enriched in differentiated epithelial-like tumors of the breast and ovary. We further show that this CNA signature translates into expected altered patterns of transcription. In addition, we show that 2 out of 12 clones analyzed were capable of anchorage-independent growth, suggesting acquisition of sufficient oncogenic transformation properties. Analysis of the CNA profile of these clones provides a potential mechanism for cyclin E-mediated oncogenesis. In order to determine whether cyclin E expression produces a specific genome-wide copy number alteration (CNA) signature, Chromosomal Microarray (CMA) analysis was carried out on DNA from individual clones. CNA call analysis of the CMA data from 12 cyclin E-overexpressing clones and 7 control clones (expressing GFP) was performed to generate a cyclin E-mediated CNA profile.