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Prostate cancer genomics

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Abstract

The molecular processes contributing to cancer of the human prostate gland are under intensive investigation. Methods used for discovering genetic alterations involved in prostate neoplasia include family studies designed to map hereditary disease loci, chromosomal studies to identify aberrations that may locate oncogenes or tumor suppressor genes, and comprehensive gene expression studies. These studies determine how various molecular signaling pathways influence or reflect the process of carcinogenesis. However, a comprehensive overview of the cell is necessary to understand all of the dynamic interactions between genes, their protein products, and the network of cellular processes resulting in tumorigenesis. Unraveling the complexity of these systems in a timely manner involves the integration of computers, miniaturization, and automation into molecular biology. New biotechnologies such as the development of automated DNA sequencing and complementary DNA microarrays allow for a systematic, “discoverydriven” approach. These and other technologies afford a comprehensive view of biology and pathology that have the potential to fully characterize the processes involved in neoplasia and therefore provide potential targets for the therapy of prostate and other cancers.

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References and Recommended Reading

  1. Landis SH, Murray T, Bolden S, Wingo PA: Cancer statistics. CA Cancer J Clin 1999, 49:8–31.

    PubMed  CAS  Google Scholar 

  2. Whittemore AS, Wu AH, Kolonel LN, et al.: Family history and prostate cancer risk in black, white, and Asian men in the United States and Canada. Am J Epidemiol 1995, 14:732–740.

    Google Scholar 

  3. Fincham SM, Hill GB, Hanson J, Wijayasinghe C: Epidemiology of prostatic cancer: a case-control study. Prostate 1990, 17:189–206.

    Article  PubMed  CAS  Google Scholar 

  4. Carter BS, Steinberg GD, Beaty TH, et al.: Familial risk factors for prostate cancer. Cancer Surv 1991, 11:5–13.

    PubMed  CAS  Google Scholar 

  5. Carter BS, Beaty TH, Steinberg GD, et al.: Mendelian inheritance of familial prostate cancer. Proc Natl Acad Sci U S A 1992, 89:3367–3371.

    Article  PubMed  CAS  Google Scholar 

  6. Carter BS, Bova GS, Beaty TH, et al.: Hereditary prostate cancer: epidemiologic and clinical features. J Urol 1993, 150:797–802.

    PubMed  CAS  Google Scholar 

  7. Goldgar DE, Easton DF, Cannon-Albright LA, Skolnick MH: Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst 1994, 86:1600–1608.

    Article  PubMed  CAS  Google Scholar 

  8. Smith JR, Freije D, Carpten JD, et al.: Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search. Science 1996, 274:1371–1374.

    Article  PubMed  CAS  Google Scholar 

  9. Hsieh CL, Oakley-Girvan I, Gallagher RP, et al.: Re: prostate cancer susceptibility locus on chromosome 1q: a confirmatory study. J Natl Cancer Inst 1997, 89:1893–1894.

    Article  PubMed  CAS  Google Scholar 

  10. Cooney KA, McCarthy JD, Lange E, et al.: Prostate cancer susceptibility locus on chromosome 1q: a confirmatory study. J Natl Cancer Inst 1997, 89:955–959.

    Article  PubMed  CAS  Google Scholar 

  11. McIndoe RA, Stanford JL, Gibbs M, et al.: Linkage analysis of 49 high-risk families does not support a common familial prostate cancer-susceptibility gene at 1q24-25. Am J Hum Genet 1997, 61:347–353.

    PubMed  CAS  Google Scholar 

  12. Eeles RA, Durocher F, Edwards S, et al.: Linkage analysis of chromosome 1q markers in 136 prostate cancer families. The Cancer Research Campaign/British Prostate Group U.K. Familial Prostate Cancer Study Collaborators. Am J Hum Genet 1998, 62:653–658.

    Article  PubMed  CAS  Google Scholar 

  13. Berthon P, Valeri A, Cohen-Akenine A, et al.: Predisposing gene for early-onset prostate cancer, localized on chromosome 1q42.2–43. Am J Hum Genet 1998, 62:1416–1424.

    Article  PubMed  CAS  Google Scholar 

  14. Goode EL, Stanford JL, Chakrabarti L, et al.: Linkage analysis of 150 high-risk prostate cancer families at 1q24-25. Genet Epidemiol 2000, 18:251–275.

    Article  PubMed  CAS  Google Scholar 

  15. Gibbs M, Chakrabarti L, Stanford JL, et al.: Analysis of chromosome 1q42.2-43 in 152 families with high risk of prostate cancer. Am J Hum Genet 1999, 64:1087–1095.

    Article  PubMed  CAS  Google Scholar 

  16. Xu J, Meyers D, Freije D, et al.: Evidence for a prostate cancer susceptibility locus on the X chromosome. Nat Genet 1998, 20:175–179.

    Article  PubMed  CAS  Google Scholar 

  17. Gibbs M, Stanford JL, McIndoe RA, et al.: Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36. Am J Hum Genet 1999, 64:776–787.

    Article  PubMed  CAS  Google Scholar 

  18. Li J, Yen C, Liaw D, et al.: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997, 275:1943–1947. This article describes the use of representational difference analysis to isolate the tumor suppressor gene PTEN. The authors describe finding mutations of the PTEN gene in multiple cancer lines. There is also a predicted protein tyrosine kinase function and a possible membrane interaction.

    Article  PubMed  CAS  Google Scholar 

  19. Steck PA, Pershouse MA, Jasser SA, et al.: Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet 1997, 15:356–362.

    Article  PubMed  CAS  Google Scholar 

  20. Li DM, Sun H: TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res 1997, 57:2124–2129.

    PubMed  CAS  Google Scholar 

  21. Lisitsyn N, Wigler M: Cloning the differences between two complex genomes. Science 1993, 259:946–951.

    Article  PubMed  CAS  Google Scholar 

  22. Lee JO, Yang H, Georgescu MM, et al.: Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association. Cell 1999, 99:323–334. This paper elegantly describes the crystal structure of PTEN and confirms a phosphatase domain as predicted. It also predicts the mechanism of action for PTEN. There is a phospholipid membrane binding domain in vitro that decreases in affinity when there are mutations of basic residues, thus possibly mitigating its ability to suppress tumor cell growth.

    Article  PubMed  CAS  Google Scholar 

  23. Giri D, Ittmann M: Inactivation of the PTEN tumor suppressor gene is associated with increased angiogenesis in clinically localized prostate carcinoma. Hum Pathol 1999, 30:419–424.

    Article  PubMed  CAS  Google Scholar 

  24. Fields C, Adams MD, White O, Venter JC: How many genes in the human genome? Nat Genet 1994, 7:345–346.

    Article  PubMed  CAS  Google Scholar 

  25. Bishop JO, Morton JG, Rosbash M, Richardson M: Three abundance classes in HeLa cell messenger RNA. Nature 1974, 250:199–204.

    Article  PubMed  CAS  Google Scholar 

  26. Adams MD, Kelley JM, Gocayne JD, et al.: Complementary DNA sequencing: expressed sequence tags and human genome project. Science 1991, 252:1651–1656.

    Article  PubMed  CAS  Google Scholar 

  27. Vasmatzis G, Essand M, Brinkmann U, et al.: Discovery of three genes specifically expressed in human prostate by expressed sequence tag database analysis. Proc Natl Acad Sci U S A 1998, 95:300–304. This paper describes the use of expressed sequence tags (ESTs) to select novel genes that are specific to prostate tissues.

    Article  PubMed  CAS  Google Scholar 

  28. Lin B, Ferguson C, White JT, et al.: Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2. Cancer Res 1999, 59:4180–4184.

    PubMed  CAS  Google Scholar 

  29. Strausberg RL, Dahl CA, Klausner RD: New opportunities for uncovering the molecular basis of cancer. Nat Genet 1997, 15:415–416.

    Article  PubMed  CAS  Google Scholar 

  30. Zhang L, Zhou W, Velculescu VE, et al.: Gene expression profiles in normal and cancer cells. Science 1997, 276:1268–1272. This paper was written by the group who first described serial analysis of gene expression in 1995. Using this method, they analyzed over 300,000 transcripts from at least 45,000 different genes, and, although they found extensive similarity between the expression profiles, there were more than 500 transcripts that were significantly differentially expressed between normal and neoplastic cells.

    Article  PubMed  CAS  Google Scholar 

  31. Emmert-Buck MR, Bonner RF, Smith PD, et al.: Laser capture microdissection. Science 1996, 274:998–1001.

    Article  PubMed  CAS  Google Scholar 

  32. Schuler GD: Pieces of the puzzle: expressed sequence tags and the catalog of human genes. J Mol Med 1997, 75:694–698.

    Article  PubMed  CAS  Google Scholar 

  33. Strausberg RL, Buetow KH, Emmert-Buck MR, Klausner RD: The cancer genome anatomy project: building an annotated gene index. Trends Genet 2000, 16:103–106. This is a current overview of the Cancer Genome Anatomy Project with a reflection on the accomplishments and a look forward to future goals, as well as the role CGAP plays in designing microarray projects.

    Article  PubMed  CAS  Google Scholar 

  34. Buetow KH, Edmonson MN, Cassidy AB: Reliable identification of large numbers of candidate SNPs from public EST data. Nat Genet 1999, 21:323–325.

    Article  PubMed  CAS  Google Scholar 

  35. Hawkins V, Doll D, Bumgarner R, et al.: PEDB: the Prostate Expression Database. Nucleic Acids Res 1999, 27:204–208. This paper gives a comprehensive description of the Prostate Expression Database and other utilities at the website (http:// www.pedb.org/) for researchers of prostate genomics.

    Article  PubMed  CAS  Google Scholar 

  36. Nelson PS, Clegg N, Eroglu B, et al.: The prostate expression database (PEDB): status and enhancements in 2000. Nucleic Acids Res 2000, 28:212–213.

    Article  PubMed  CAS  Google Scholar 

  37. Chee M, Yang R, Hubbell E, et al.: Accessing genetic information with high-density DNA arrays. Science 1996, 274:610–614.

    Article  PubMed  CAS  Google Scholar 

  38. Schena M, Shalon D, Davis RW, Brown PO: Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 1995, 270:467–470.

    Article  PubMed  CAS  Google Scholar 

  39. Nguyen C, Rocha D, Granjeaud S, et al.: Differential gene expression in the murine thymus assayed by quantitative hybridization of arrayed cDNA clones. Genomics 1995, 29:207–216.

    Article  PubMed  CAS  Google Scholar 

  40. Nelson PS, Han D, Rochon Y, et al.: Comprehensive analyses of prostate gene expression: convergence of expressed sequence tag databases, transcript profiling and proteomics. Electrophoresis 2000, 21:1823–1831.

    Article  PubMed  CAS  Google Scholar 

  41. Blanchard AP, Hood L: Sequence to array: probing the genome’s secrets. Nat Biotechnol 1996, 14:1649.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Mailstop D4-100, 98109-1024, Seattle, WA, USA

    Paul E. Li MD & Peter S. Nelson MD

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  1. Paul E. Li MD
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  2. Peter S. Nelson MD
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Li, P.E., Nelson, P.S. Prostate cancer genomics. Curr Urol Rep 2, 70–78 (2001). https://doi.org/10.1007/s11934-001-0028-6

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  • DOI: https://doi.org/10.1007/s11934-001-0028-6

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