Genomic Instability in Sporadic Colorectal Cancer

A Destabilized Genome Producing Accelerated Cellular Evolution as the Fundamental Nature of Cancer
  • Garth R. Anderson
  • Daniel L. Stoler
  • Morton S. Kahlenberg
  • Nicholas J. Petrelli
Part of the Pezcoller Foundation Symposia book series (PFSO, volume 9)

Abstract

Two major forms of genomic alterations are seen abundantly in solid tumors (1). The predominant form is intrachromosomal genomic instability, which manifests itself as deletions, insertions, amplifications and translocations (2). The molecular basis of this form of instability has not been established, and recent evidence indicates p53 is unlikely to be involved here (3). A common feature of this major type of instability is an early role for DNA breakage, suggesting nuclease involvement. Aneuploidy produces gains or losses of entire chromosomes, in a process involving p53 and inappropriate meiotic-like segregation (5). Microsatellite instability represents a less common third type of genomic instability which produces oligonucleotide insertions or deletions within repetitive sequences; this is most often seen in hereditary cancer syndromes (e.g. HNPCC), where it somehow tends to preclude the appearance of the other types of instability (6).

Keywords

Entropy Expense Noma Gordenin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kastan, M.B., ed. Genetic Instability and Tumorigenesis. Current Topics in Microbiology and Immunology. Volume 221, 1997.Google Scholar
  2. 2.
    Barrett, J.C., Tsutsui, T., Tlsty, T. and Oshimura, M. Genetic mechanisms in carcinogenesis and tumor progression. C.C. Harris and L.A. Liotta, eds. Wiley-Liss, NY. pp. 97–114, 1990.Google Scholar
  3. 3.
    Kahlenberg, M.S., Stoler, D.L., Basik, M., Petrelli, N.J., Rodriguez-Bigas, M. and Anderson, G.R. p53 tumor suppressor gene status and the degree of genomic instability in sporadic colorectal cancers. J. Natl. Cancer Inst. 88: 1665–1670, 1996.PubMedCrossRefGoogle Scholar
  4. 4.
    Fishel, R. Genomic instability, mutators and the development of cancer: is there a role for p53? J. Natl. Cancer Inst. 88: 1608–1609, 1996.PubMedCrossRefGoogle Scholar
  5. 5.
    Fukasawa, K., Choi, T., Kuriyama, R., Rulong, S. and Vande Woude, G.F. Abnormal centrosome amplification in the absence of p53. Science 271: 1744–1747, 1996.PubMedCrossRefGoogle Scholar
  6. 6.
    Liu, B., Nicolaides, N.C., Markowitz, S., Willson, J.K.V., Parsons, R.E., Jen, J., Papadopolous, N., Peltomaki, P., de la Chapelle, A., Hamilton, S.R., Kinzler, K.W. and Vogelstein, B. Mismatch repair gene defects in sporadic colorectal cancers with microsatellite instability. Nature Genetics 9: 48–55, 1995.PubMedCrossRefGoogle Scholar
  7. 7.
    Basik, M., Stoler, D.L., Kontzoglou, K.C., Rodriguez-Bigas, M.A., Petrelli, N.J. and Anderson, G.R. Genomic instability in sporadic colorectal cancer quantitated by inter-simple sequence repeat PCR analysis. Genes, Chromosomes and Cancer 18: 19–29, 1997.CrossRefGoogle Scholar
  8. 8.
    Kallioniemi, O.P., Kallioniemi, A., Sudar, D., Rutovitz, D., Graw, J.W., Waldman, F. and Pinkel, D. Comparative genomic hybridization: a rapid new method for detecting and mapping DNA amplification in tumors. Sem. Cancer Biol. 4: 41–46, 1993.Google Scholar
  9. 9.
    Gordenin, D.A., Lobachev, K.S., Degtyareva, N.P., Malkova, A.L., Perkins, E., Resnick, M.A. Inverted DNA repeats: a source of eukaryotic genomic instability. Mol. Cell. Biol. 13: 5315–5322, 1993.PubMedGoogle Scholar
  10. 10.
    Russo, CA., Weber, T.K., Volpe, CM., Stoler, D.L., Petrelli, N.J., Rodriguez-Bigas, M., Burhans, W.C and Anderson, G.R. The anoxia-inducible endonuclease and enhanced DNA breakage as contributors to genomic instability in cancer. Cancer Res. 55: 1122–1128, 1995.PubMedGoogle Scholar
  11. 11.
    Anderson, G.R., Volpe, CM., Russo, CA., Stoler, D.L. and Miloro, S.M. The anoxic fibroblast response: a cellular program utilized during early stage wound healing. J. Surg. Res. 59: 666–674, 1995.PubMedCrossRefGoogle Scholar
  12. 12.
    Mewes, H.W., Albermann, K., Bahr, M., Frishman, D., Gleissner, A., Hani, J., Heumann, K., Kleine, K., Maierl, A., Oliver, S.G., Pfeiffer, F. and Zollner, A. Overview of the yeast genome. Nature 387: 7–9, 1997.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Garth R. Anderson
    • 1
    • 2
  • Daniel L. Stoler
    • 1
  • Morton S. Kahlenberg
    • 2
  • Nicholas J. Petrelli
    • 2
  1. 1.Department of Molecular and Cellular BiologyRoswell Park Cancer InstituteBuffaloUSA
  2. 2.Department of Surgical OncologyRoswell Park Cancer InstituteBuffaloUSA

Personalised recommendations