Genomic Instability and DNA Repair

Abstract There is growing evidence that genomic instability is both an epiphenomenon and a leading cause of cancer. Chromosomal instability in neoplasia (CIN) is the most frequent type of genomic instability in solid tumours. For more than a century, chromosomal rearrangements and aneuploidy in neoplasia have been extensively studied and a vast number of genes and pathways, directly or indirectly implicated in CIN, have been described. Chromosomal abnormalities in cancer generate huge genomic imbalances and tumour heterogeneity. This chapter addresses the role of genes, chromosome structure, and telomere dysfunction in the initiation and perpetuation of CIN. The biological consequences of large chromosomal imbalances are discussed and the long‐standing hypotheses for the generation of chromosomal anomalies in neoplasia are re‐examined under the context of telomere dysfunction and restoration.