Abstract
Tumor suppressor genes (TSGs) are genes whose protein products function in the control of cellular proliferation. In contrast to oncogenes, which are activated in cancer, TSGs are functionally inactivated in cancer. In general, TSGs are characterized by loss-offunction mutations in human tumors. These loss-of-fuunction mutations can be missense mutations that alter critical amino acid residues, mutations that cause premature protein truncation resulting in the loss of functional domains or unstable products, or deletion of the entire gene. Loss-of-function mutations are often accompanied by loss of heterozygosity (LOH) at the TSG locus; LOH can be detected by comparing the pattern of a polymorphic DNA marker in tumor versus normal DNA (see Chapter 1).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Knudson A: Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971, 68: 820–823.
Clurman B, Groudine M: Defining tumour-suppressor genes. Nature 1997, 389: 123.
Haber D, Harlow E: Tumour-suppressor genes: evolving definitions in the genomic age. Nat Genet 1997, 16: 320–322.
Knudson A: Antioncogenes and human cancer. Proc Natl Acad Sci USA 1993, 90: 10914–10921.
Neumann H, Lips C, Hsia Y, Thar B: Von HippelLindau syndrome. Brain Patho11995, 5: 181–193.
Prowse A, Webster A, Richards F,: Somatic inactivation of the VHL gene in von Hippel-Lindau disease tumors. Am J Hum Genet 1997, 60: 765–771.
Foster K, Prowse A, van den Berg A,: Somatic mutations of the von Hippel-Lindau disease TSG in non-familial clear cell renal carcinoma. Hum Mol Genet 1994, 3: 2169–2173.
Fearon E, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 1990, 61: 759–767.
Kinzler K, Vogelstein B: Gatekeepers and caretakers. Nature 1997, 386: 761–763.
Moslein G, Tester D, Lindor N,: Microsatellite instability and mutation analysis of hMSH2 and HMLH1 in patients with sporadic, familial and hereditary colorectal cancer. Hum Mol Genet 1996, 5: 1245–1252.
Neumann H, Bender B: Genotype-phenotype correlations in von Hippel-Lindau disease. J Intern Med 1998, 243: 541–545.
Spirio L, Olschwant S, Groden J,: Alleles of the APC gene: an attenuated form of familial polyposis. Cell 1993, 75: 951–957.
Gutmann D, Geist R, Xu H,: Defects in neurofibromatosis 2 protein function can arise at multiple levels. Hum Mol Genet 1998, 7: 335–345.
Lin S-C, Skapek S, Lee E-H: Genes in the RB pathway and their knockout in mice. Semin Cancer Biol 1996, 7: 279–289.
Jacks T, Weinberg R: The expanding role of cell cycle regulators. Science 1998, 280: 1035.
Hesketh R: The Oncogene and Tumor Suppressor Gene Facts Book. San Diego, CA: Academic Press; 1997.
Chin L, Pomerantz J, DePinho R: The INK4a/ARF tumor suppressor: one gene, two products, two pathways. TIBS 1998, 23: 291.
Helin K, Peters G: Tumor suppressors: from genes to function and possible therapies. Trends Genet 1998, 14: 8–9.
Reynisdottir I, Polyak K, Iavarone A, Masague J: Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-5. Genes Dey 1995, 9: 1931–1945.
Kolodner R: Mismatch repair: mechanisms and relationship to cancer susceptibility. TIBS 1995, 20: 397.
Kolodner R: Biochemistry and genetics of eukaryotic mismatch repair. Genes Dey 1996, 10: 1433–1442.
Prolla T, Abruin A, Bradley A: DNA mismatch repair deficient mice in cancer research. Semin Cancer Biol 1996, 7: 241–247.
Karran P: Appropriate partners make good matches. Science 1995, 268: 1857.
Kunkel T, Resnick M, Gordenin D: Mutators specificity and disease: looking over the FENce. Cell 1997, 88: 155–158.
Marsischky G, Filosi M, Kane M, Kolodner R: Redundancy of saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair. Genes Dey 1996, 10: 407–429.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Current Medicine, Inc.
About this chapter
Cite this chapter
Plank, T.L., Henske, E.P. (2000). Tumor Suppressor Genes. In: Kruh, G.D., Tew, K.D. (eds) Basic Science of Cancer. Current Medicine Group. https://doi.org/10.1007/978-1-4684-8437-3_3
Download citation
DOI: https://doi.org/10.1007/978-1-4684-8437-3_3
Publisher Name: Current Medicine Group
Print ISBN: 978-1-4684-8439-7
Online ISBN: 978-1-4684-8437-3
eBook Packages: Springer Book Archive