Abstract
Allelic loss of human chromosome sequences contributes to tumorigenesis through the inactivation of putative tumor-suppressor genes. The Knudson hypothesis proposes that deletion or mutation must affect both alleles of the gene in order to disable tumor suppression (1). As might be expected, the effect of “two hits” on tumor-suppressor gene integrity—e.g., deletion of one allele and mutation of the remaining allele—would disable the gene from encoding gene product. The von Hippel-Lindau (VHL) gene is an example of a tumorsuppressor gene that fulfills the Knudson hypothesis—e.g., one mutant allele is inherited in the germline, and the other is mutated or deleted somatically in many clear-cell renal cell carcinomas (recently reviewed in ref.2).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Knudson, A. G., Jr. (1971) Mutation and cancer: statistical study of retinoblastoma. Proc. Natl. Acad. Sci. USA68, 820–823.
Kaelin, W. G. and Maher, E. R. (1998) The VHL tumour-suppressor gene paradigm. Trends Genet.14, 423–426.
Sambrook, J., Fritsch, E. F., and Maniatis, T., eds. (1989) The polymerase chain reaction, in Molecular Cloning: A Laboratory Manual. 2nd Ed. ) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 14.1–14.35.
Saiki, R. K. (1990) Amplification of Genomic DNA, in PCR Protocols: A Guide to Methods and Applications (Innis, M. A., Gelfand, D. H., Sninsky J. J., and White, T. J., eds.), Academic Press, Inc., New York, pp. 13–20.
Kramer, M. F. and Coen, D. M. (1995) The polymerase chain reaction, in Current Protocols in Molecular Biology. (Ausubel, F. M., Brent, R., Kingston, R. E., Moore, D. D., Seidman, J. G., Smith, J. A., and Struhl, K., eds.) John Wiley and Sons, NewYork, pp. 15.0.1–15.8.8.
Weber, J. L. (1989) Length polymorphisms in (dC-dA)n.(dG-dT)n sequences using the polymerase chain reaction, in Current Communications in Molecular Biology: Polymerase Chain Reaction (Erlich,. A., Gibbs, R., and Kazazian, H. H., Jr., eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 141–150.
Trybus, T. M., Burgess, A. C., Wojno, K. J., Glover, T. W., and Macoska, J. A. (1996) Distinct Areas of Allelic Loss on Chromosomal Regions 10p and 10q in Human Prostate Cancer. Cancer Res.56, 2263–2267.
Prasad, M. A., Wojno, K. J., and Macoska, J. A. (1998) Homozygous and frequent deletion of proximal 8p sequences in human prostate cancers: identification of a potential tumor suppressor gene site. Genes Chromosomes Cancer23, 255–262.
MacGrogan, D., Levy, A., Bostwick, D., Wagner, M., Wells, D., and Bookstein, R. (1994) Loss of chromosome arm 8p loci in prostate cancer: Mapping by quantitative allelic imbalance Genes Chromosomes Cancer10, 151–159.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Humana Press Inc.
About this protocol
Cite this protocol
Macoska, J.A. (2001). Polymerase Chain Reaction Detection of DNA Sequence Deletions. In: Mydlo, J.H. (eds) Renal Cancer. Methods in Molecular Medicine, vol 53. Humana, Totowa, NJ. https://doi.org/10.1385/1-59259-144-2:125
Download citation
DOI: https://doi.org/10.1385/1-59259-144-2:125
Publisher Name: Humana, Totowa, NJ
Print ISBN: 978-0-89603-828-8
Online ISBN: 978-1-59259-144-2
eBook Packages: Springer Protocols