Chromosomal
aneuploidies are observed in essentially all sporadic
carcinomas. These
aneuploidies result in
tumor-specific patterns of genomic imbalances that are acquired early during
tumorigenesis, continuously selected for and faithfully maintained in
cancer cells. Although the paradigm of translocation induced oncogene activation in
hematologic malignancies is firmly established, it is not known how genomic imbalances affect chromosome-specific gene expression patterns in particular and how chromosomal
aneuploidy dysregulates the genetic equilibrium of cells in general. To model specific chromosomal
aneuploidies in
cancer cells and dissect the immediate consequences of genomic imbalances on the transcriptome, we generated artificial
trisomies in a karyotypically stable diploid yet mismatch repair-deficient,
colorectal cancer cell line and in
telomerase immortalized, cytogenetically normal human breast epithelial cells using microcell-mediated chromosome transfer. The global consequences on gene expression levels were analyzed using
cDNA arrays. Our results show that regardless of chromosome or cell type, chromosomal
trisomies result in a significant increase in the average transcriptional activity of the trisomic chromosome. This increase affects the expression of numerous genes on other chromosomes as well. We therefore postulate that the genomic imbalances observed in
cancer cells exert their effect through a complex pattern of transcriptional dysregulation.