Aneuploidy, the unbalanced state of the chromosome content, represents a hallmark of most solid tumors. Such aneuploidies result in tumor specific genomic imbalances, which emerge in premalignant precursor lesions. Moreover, increasing levels of chromosomal instability have been observed in adenocarcinomas and are maintained in distant metastases. A number of studies have systematically integrated copy number alterations with gene expression changes in primary carcinomas, cell lines, and experimental models of aneuploidy. In fact, chromosomal aneuploidies target a number of genes conferring a selective advantage for the metabolism of the cancer cell. Copy number alterations not only have a positive correlation with expression changes of the majority of genes on the altered genomic segment, but also have effects on the transcriptional levels of genes genome-wide. Finally, copy number alterations have been associated with disease outcome; nevertheless, the translational applicability in clinical practice requires further studies. Here we review (i) the spectrum of genetic alterations that lead to solid tumors, (ii) the most frequent copy number alterations at different stages of cancer, (iii) exemplify their positive correlation with gene expression levels, and (iv) discuss copy number alterations that are potentially involved in disease outcome of individual patients.

Dr. Ried received his M.D. from the Max Planck Institute for Medical Research in Heidelberg, Germany. After having completed his postdoctoral training at the University of Leiden and at Yale University, he joined the faculty of the National Human Genome Research Institute in 1994. Dr. Ried became an investigator at the NCI in 1998 and a senior investigator and Chief of the Cancer Genomic Section in 2002. Since 1998 he has co-directed the Cancer Chromosome Aberration Project. In 2000, Dr. Ried received the AMGEN award of the American Society of Biochemistry and Molecular Biology. Dr. Ried serves as a member of the editorial board for numerous scientific journals.