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Because the genome exerts control for cellular function, maintaining genome stability is important for the continued function of cells, tissues, and organisms. DNA is the carrier of genetic information. Its structure is regularly threatened by damaging agents that include oxidative stress, ultraviolet (UV) and X-radiation, and chemical agents. Although much damage is repaired, failure to maintain genomic integrity may lead to abnormal cell function or cell death. If the cell divides, progeny may accumulate additional damage and this progressive accumulation of damage can lead to malignancy (see Chapter 110).
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This chapter describes the relevant skin disorders with genome instability and the underlying defective mechanisms of DNA repair or DNA maintenance (Tables 139-1 and 139-2). All of these exhibit prominent cutaneous abnormalities that involve dermatologists in their diagnosis and management. Most, but not all, are also characterized by an increased risk of malignancies. This demonstrates that the maintenance of genome integrity is of utmost importance for the prevention of malignant transformation. Malignant transformation requires the accumulation of several mutations in specific genes of a single cell. Thus a mutator phenotype is often regarded a prerequisite for carcinogenesis, because without genome instability it would be exceedingly unlikely that all of those mutations occur in a single cell.1–4 The same genes that are affected in the hereditary genome instability disorders can also confer genome instability to individual cells when impaired through acquired mutations, thereby playing an important role early in spontaneous carcinogenesis.
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