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Chromosomal deletions and tumor suppressor genes in prostate cancer

  • Chapter
Book cover Prostate Cancer: New Horizons in Research and Treatment

Part of the book series: Developments in Oncology ((DION,volume 81))

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Abstract

Chromosomal deletion appears to be the earliest as well as the most frequent somatic genetic alteration during carcinogenesis. It inactivates a tumor suppressor gene in three ways, that is, revealing a gene mutation through loss of heterozygosity as proposed in the two-hit theory, inducing haploinsufficiency through quantitative hemizygous deletion and associated loss of expression, and truncating a genome by homozygous deletion. Whereas the two-hit theory has guided the isolation of many tumor suppressor genes, the haploinsufficiency hypothesis seems to be also useful in identifying target genes of chromosomal deletions, especially for the deletions detected by comparative genomic hybridization (CGH). At present, a number of chromosomal regions have been identified for their frequent deletions in prostate cancer, including 2q13\2-q33, 5q14\2-q23, 6q16\2-q22, 7q22\2-q32, 8p21\2-p22, 9p21\2-p22, 10q23\2-q24, 12p12\2-13, 13q14\2-q21, 16q22\2-24, and 18q21\2-q24. Strong candidate genes have been identified for some of these regions, including NKX3.1 from 8p21, PTEN from 10q23, p27/Kipl from 12p13, and KLF5 from 13q21. In addition to their location in a region with frequent deletion, there are functional and/or genetic evidence supporting the candidacy of these genes. Thus far PTEN is the most frequently mutated gene in prostate cancer, and KLF5 showed the most frequent hemizygous deletion and loss of expression. A tumor suppressor role has been demonstrated for NKX3.1, PTEN, and p27/Kipl in knockout mice models. Such genes are important targets of investigation for the development of biomarkers and therapeutic regimens.

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Authors and Affiliations

  1. Department of Pathology, Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, VA, USA

    Jin-Tang Dong

  2. Department of Pathology, University of Virginia Health System, Box 800214, Charlottesville, Virginia, 22908, USA

    Jin-Tang Dong

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  1. Jin-Tang Dong
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Editors and Affiliations

  1. The Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA

    Michael L. Cher

  2. Wayne State University School of Medicine, Detroit, MI, USA

    Avraham Raz  & Kenneth V. Honn  & 

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© 2002 Kluwer Academic Publishers

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Dong, JT. (2002). Chromosomal deletions and tumor suppressor genes in prostate cancer. In: Cher, M.L., Raz, A., Honn, K.V. (eds) Prostate Cancer: New Horizons in Research and Treatment. Developments in Oncology, vol 81. Springer, Boston, MA. https://doi.org/10.1007/0-306-48143-X_4

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  • DOI: https://doi.org/10.1007/0-306-48143-X_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4020-7352-6

  • Online ISBN: 978-0-306-48143-7

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