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Aneuploidy is a defining feature of epithelial cancers with an impact on the genesis, progression and prognosis of these malignancies. Essentially all sporadic, mismatch repair proficient colorectal carcinomas are defined by a non-random distribution of genomic imbalances. Regarding breast cancer, however, aneuploid and near diploid cases show almost similar frequencies. Independent of the tumor entity, increased levels of aneuploidy result in a worse clinical outcome. For breast and colorectal carcinomas, aneuploidy has been reported as an independent prognostic factor with an impact comparable to that of the tumor stage. Unfortunately, the translation of this knowledge into the clinic was slow. Prognostication in breast cancer is augmented by gene expression profiles of poor or good prognosis. Interestingly, there is growing evidence that prognostic gene expression signatures simply reflect the degree of genomic instability. This is not surprising since gross nuclear aneuploidy is reflected in a strikingly recurrent and tumor entity specific distribution of chromosomal imbalances. Chromosomal imbalances, in turn, do significantly modulate resident gene expression levels. Furthermore, aneuploidy also affects protein expression. Proteomics has therefore become a powerful tool to unravel potential new targets for diagnostics, prognostication and therapeutic stratification. There is also increasing evidence that aneuploidy precedes invasive disease and can already be detected in premalignant lesions such as colon adenomas and/or ulcerative colitis. It is therefore reasonable to assume that aneuploidy plays a crucial role during carcinogenesis, an interpretation consistent with its direct influence on disease outcome. This has triggered considerable efforts to elucidate how aneuploidy develops and what its impact is on the genetic equilibrium of cells at the molecular level.

Aneuploidy and Epithelial Cancers: The Impact of Aneuploidy on the Genesis, Progression and Prognosis of Colorectal and Breast Carcinomas