Mutation Accumulation In Vivo and the Importance of Genome Stability in Aging and Cancer
Somatic mutations are generally considered as the major cause of cancer. This can be derived from various observations, including the actual presence of mutations in the tumor genome in genes thought to be critically involved in tumor initiation and/or progression, such as TP53,KRAS, and RB1 (Lengauer et al. 1998). Both exogenous (Greenblatt et al. 1994) and endogenous (Jackson et al. 1998) mutagenic mechanisms have been implicated in the induction of these mutations. Modeling of such gene defects into the mouse genome often results in accelerated tumorigenesis (Vijg and van Steeg 1998), confirming the critical role of specific mutations as a cause of cancer. Other indirect evidence involves the general observation that most, if not all, mutagens are also carcinogens and that heritable mutations in genes controlling genome stability pathways often confer a high cancer susceptibility (Vijg and van Steeg 1998).
KeywordsSomatic Mutation Nucleotide Excision Repair Genome Stability Xeroderma Pigmentosum Mutation Accumulation
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