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Cancer: Cell Structures, Carcinogens and Genomic Instability pp 303–320Cite as

Genetic instability in human tumors

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Part of the book series: Experientia Supplementum ((EXS,volume 96))

Abstract

Genetic, or genomic, instability refers to a series of observed spontaneous genetic changes occurring at an accelerated rate in cell populations derived from the same ancestral precursor. This is far from a new finding, but is one that has increasingly gained more attention in the last decade due to its plausible role(s) in tumorigenesis. The majority of genetic alterations contributing to the malignant transformation are seen in growth regulatory genes, and in genes involved in cell cycle progression and arrest. Genomic instability may present itself through alterations in the length of short repeat stretches of coding and non-coding DNA, resulting in microsatellite instability. Tumors with such profiles are referred to as exhibiting a mutator phenotype, which is largely a consequence of inactivating mutations in DNA damage repair genes. Genomic instability may also, and most commonly, results from gross chromosomal changes, such as translocations or amplifications, which lead to chromosomal instability. Telomere length and telomerase activity, important in maintaining chromosomal structure and in regulating a normal cell’s lifespan, have been shown to have a function in both suppressing and facilitating malignant transformation. In addition to such direct sequence and structural changes, gene silencing through the hypermethylation of promoter regions, or increased gene expression through the hypomethylation of such regions, together, form an alternative, epigenetic mechanism leading to instability. Emerging evidence also suggests that dietary and environmental agents can further modulate the contribution of genetic instability to tumorigenesis. Currently, there is still much debate over the distinct classes of genomic instability and their specific roles in the initiation of tumor formation, as well as in the progressive transition to a cancerous state. This review examines the various molecular mechanisms that result in this genomic instability and the potential contribution of the latter to human carcinogenesis.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada

    Stavroula Raptis & Bharati Bapat

  2. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada

    Stavroula Raptis & Bharati Bapat

  3. Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A1, Canada

    Stavroula Raptis & Bharati Bapat

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Raptis, S., Bapat, B. (2006). Genetic instability in human tumors. In: Cancer: Cell Structures, Carcinogens and Genomic Instability. Experientia Supplementum, vol 96. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7378-4_13

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