Skip to main content
SpringerLink
Log in

The Cloning of Tumor Suppressor Genes from the Short Arm of Human Chromosome 3 that Play a Role in the Development of Renal Cell Carcinoma

  • Conference paper
Biology of Renal Cell Carcinoma

  • 46 Accesses

Abstract

Specific rearrangements involving chromosome 3 have been described in several malignant disorders, most notably in lung cancer and renal cell carcinoma (RCC). In these tumors, deletions or non-reciprocal translocations resulting in the loss of short arm material have been demonstrated in a majority of cases (1,2). At the molecular level, loss of 3p heterozygosity has corroborated these cytogenetic changes (2–4). The introduction of a normal chromosome 3p into a human renal cell carcinoma cell line modulated the tumorigenicity of these cells (5) demonstrating that there are gene(s) on chromosome 3p that may function as tumor suppressors. However, evidence is accumulating that there are multiple tumor suppressor loci on chromosome 3p: a tumor suppressor in 3p13–p14 (6,7), a tumor suppressor in 3p21 that can slow the growth of mouse A9 cells in nude mice (8), and the Von Hippel Lindau disease (VHL) gene in 3p25 (9,10).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Whang-Peng, J., Bunn, P.A., Kao-Shan, C.S., et al. (1982)A non-random chromosomal abnormality, del 3p(14–23) in human small cell lung cancer (SCLC). Cancer Genet. Cytogenet. 6:119–134.

    Article  PubMed  CAS  Google Scholar 

  2. Kovacs, G., Erlandsson, R., Boldog, F., Ingvarsson, S., Muller-Brechlin, R., Klein, G., and Sumegi, J. (1988) Consistent chromosome 3p deletion and loss of heterozygosity in renal cell carcinoma. Proc. Natl. Acad. Sci. USA 85:1571–1575.

    Article  PubMed  CAS  Google Scholar 

  3. Brauch, H., Johnson, B., Hovis, J., et al. (1987) Molecular analysis of the short arm of chromosome 3 in small-cell and non-small cell carcinoma of the lung. New Engl. J. Med. 317:1109–1113.

    CAS  Google Scholar 

  4. Naylor, S.L., Johnson, B.E., Minna, J.D., and Sakaguchi, A.Y. (1987) Loss of heterozygosity of 3p markers in small-cell lung cancer. Nature 329:451–454.

    Article  PubMed  CAS  Google Scholar 

  5. Shimuzu, M., Yokota, J., Mori, N., Shuin, T., Shinoda, M., Terada, M., and Oshimura, M. (1990) Introduction of a normal chromosome 3p modulates the tumorigenicity of a human renal cell carcinoma cell line YCR. Oncogene 5:185194.

    Google Scholar 

  6. Cohen, A.J., Li, F.P., Berg, S., Marchetto, D.J., Tsai, S., Jacobs, S.C., and Brown, R.S. (1979) Hereditary renal-cell carcinoma associated with a chromosomal translocation. N. Engl. J. Med. 301:592–595.

    Article  PubMed  CAS  Google Scholar 

  7. Pathak, S., Strong, L.C., Ferrell, R.E., and Trinidade, A. (1982) Familial renal cell carcinoma with a 3;11 chromosome translocation limited to tumor cells. Science 217:939–941.

    Article  PubMed  CAS  Google Scholar 

  8. Kilary, A.M., Wolf, M.E., Giambernardi, T.A., and Naylor, S.L. (1992) Definition of a tumor suppressor locus within 3p21-p22. Proc. Natl. Acad. Sci. USA 89:10877–10881.

    Article  Google Scholar 

  9. Tory, K., Brauch, H., Linehan, M., et al. (1989) Specific genetic change in tumors associated with von Hippel-Lindau disease. J. Natl. Cancer Inst. 81:1097–1101.

    Article  PubMed  CAS  Google Scholar 

  10. Seizinger, B.R., Smith, D.I., Filling-Katz, M.R., et al. (1991) Genetic flanking markers refine diagnostic criteria and provide insights into the genetics of Von Hippel Lindau disease. Proc. Natl. Acad. Sci. USA 88:2864–2869.

    Article  PubMed  CAS  Google Scholar 

  11. Melmon, K.L., and Rosen, S.W. (1964) Von Hippel Lindau disease and human cancers. Am. J. Med.

    Google Scholar 

  12. Go. R.C.P., Lamiell, J.M., Hsia, Y.E., Yen, J.W.M., and Paik, Y. (1984) Segregation and linkage analyses of von Nippe 1Lindau disease among 220 descendants from one kindred. Amer. J. Hum. Genet. 36:131142.

    Google Scholar 

  13. Huson, S.M., Harper, P.S., Hourihan, M.D., Cole, G., Weeks, R.D.,and Compston, D.A.S. (1986) Cerebellar hemangioblastoma and von Hippel Lindau disease. Brain 109:1297–1310.

    Article  PubMed  Google Scholar 

  14. Lamiell, J.M., Salazar, F.G., and Hsia, Y.E. (1989) Von Hippel-Lindau disease affecting 43 members of a single kindred. Medicine 68:1–29.

    Article  PubMed  CAS  Google Scholar 

  15. Hosoe, S., Brauch, H., Latif, F., et al. (1990) Localization of the von HippelLindau disease gene to a small region of chromosome 3. Genomics 8:634–640.

    Article  PubMed  CAS  Google Scholar 

  16. Miller, Y.E., Minna, J.D., and Gazdar, A. (1989) Lack of expression of aminoacylase-1 in small cell lung cancer: evidence of inactivation of genes encoded by chromosome 3p. J. Clin. Invest. 83:2120–2124.

    Article  PubMed  CAS  Google Scholar 

  17. Kok, K., Hofstra, R., Pilz, A., et al. (1993) A gene in the chromosomal region 3p21 with greatly reduced expression in lung cancer is similar to the gene for ubiquitinactivating enzyme. Proc. Natl. Acad. Sci. USA 90:6071–6075.

    Article  PubMed  CAS  Google Scholar 

  18. Erlandsson, R., Bergerheim, U.S.R., Boldog, F., et al. (1990) A gene near the D3F 1552 site on 3p is expressed in normal human kidney but not or only a severly reduced level in 11 of 15 primary renal cell carcinomas (RCC).

    Google Scholar 

  19. Smeets, D.F.C.M., Scheres, J.M.J.C., and Hustinx, T.W.J. (1986) The most common fragile site in man is 3p14. Hum. Genet. 72:215–220.

    CAS  Google Scholar 

  20. Smith, D.I., Golembieski, W., Gilbert, J.D., Kizyma, L., and Miller, O.J. (1987) Overabundance of rare-cutting restriction endonuclease sites in the human genome. Nucl. Acids Res. 15:1173–1184.

    Article  CAS  Google Scholar 

  21. Smith, D.I., Mangrulker, R.J., Geist, R., Gilbert, J., Kinsman, K., Drabkin, H.A., and Golembieski, W.G. (1989) Saturation of human chromosome 3 with unique sequence hybridization probes. Genomics 43:442–451.

    Google Scholar 

  22. Drabkin, H., Jonsen, M., Wright, M., et al. (199) Development of a somatic cell hybrid mapping panel and molecular probes for human chromosome 3. Genomics 8:435–446.

    Article  Google Scholar 

  23. Smith, D.I., Liu, W., Ginzinger, D., et al. (1991) Localization of 616 human chromosome 3-specific cosmids using a somatic cell hybrid deletion mapping panel. Genomics 11:179–187.

    Article  PubMed  CAS  Google Scholar 

  24. Seizinger, B.R., Rouleau, G.A., Ozelius, L.J., et al. (1989) Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature 332:268–269.

    Article  Google Scholar 

  25. Bonner, T., O’Brien, S.J., Nash, W.G., Rapp, U.R., Morton, C.C., and Leder, P. (1984) The human homolgues of the raf (mil) oncogene are located on human chromosomes 3 and 4. Science 223:71–74.

    Article  PubMed  CAS  Google Scholar 

  26. Vance, J.M., Small, K., Jones M.A., et al. (1990) Confirmation of linkage in von Hippel-Lindau disease. Genomics 6:565–567.

    Article  PubMed  CAS  Google Scholar 

  27. Pericak-Vance, P., Nunes, K., Whisenant, E., et al. (1993) Genetic mapping of dinucleotide repeat polymorphisme and von Hippel Lindau disease on chromosome 3p25-p26. J. Med. Genet. 30:487–491.

    Article  PubMed  CAS  Google Scholar 

  28. Richards, F.M., Maher, E.R., Latif, F., et al. (1992)Detailed genetic mapping of von Hippel-Lindua disease. J. Med. Genet. 29:902–905.

    Article  PubMed  Google Scholar 

  29. Burke, D.T., Carle, F.G., and Olson, M.V. (1987) Cloning large segments of exogenous DNA into yeast by means of artificial chromosome vectors. Science 236:806–812.

    Article  PubMed  CAS  Google Scholar 

  30. Albertsen, H.M., ABderrahim, H., Cann, H.M., et al. (1990) Construction and characterization of a yeast artificial chromosome library containing seven haploid genome equivalents. Proc. Natl. Acad. Sci. USA 87:4256–4260.

    Article  PubMed  CAS  Google Scholar 

  31. Chumakov, I., Rigault, P., Guillou, S., et al. (1992) Continuum of overlapping clones spanning the entire human chromosome 21q. Nature 359:380–387.

    Article  PubMed  CAS  Google Scholar 

  32. Mendez, M.J., Klapholz, S., Brownstein, B.H., and Gemmill, R.M. (1991) Rapid screening of a YAC library by pulsed-field gel southern blot analysis of pooled YAC clones. Genomics 10:661–665.

    Article  PubMed  CAS  Google Scholar 

  33. Liu, W., Piechocki, M., Shridhar, V., et al. (1993) The isolation of a yeast artificial chromosome (YAC) contig extending for 2 megabases in the vicinity of the Von Hippel Lindau disease gene. Human Molec. Genet.2:1177–1182.

    CAS  Google Scholar 

  34. Latif, F., Duh, F.M., Gnarra, J., et al. (1993) Cloning and identification of the plasma membrane Ca transporting ATPase isoform 2 gene that resides in the von Hippel-Lindau disease region. Cancer Res. 53:861–867.

    PubMed  CAS  Google Scholar 

  35. Gieser, L., and Swaroop, A. (1992) Expressed sequence tags and chromosomal localization of cDNA clones from a subtracted retinal pigment epithelium library. Genomics 13 873–876.

    Article  PubMed  CAS  Google Scholar 

  36. Latif, F., Tory, K., Gnarra, J., et al. (1993) Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 260:1317–1320.

    Article  PubMed  CAS  Google Scholar 

  37. Latif, F., Gnarra, J., Tory, K., et al. (1993) Frequent germline and sporadic renal cell carcinoma mutations in Von Hippel Lindau disease tumor suppressor gene. Amer. J. Hum. Genet. 53:A318.

    Google Scholar 

  38. Tory, K., Schmidt, L., Chen, F., et al. (1993) Mutation analysis of the von HippelLindau disease (VHL) gene in carcinomas of the kidney, lung, breast and ovary. Amer. J. Hum. Genet. 53:A378.

    Google Scholar 

  39. Yokata, J., Wada, M., Simosato, Y, Masaaki, T., and Sugimura, T. (1987) Loss of heterozygosity on chromosomes 3, 13, and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung. Proc. Natl. Acad. Sci. USA 84:9252–9256.

    Google Scholar 

  40. Johnson, B.E., Sakaguchi, A.Y., Gazdar, A., Minna, J.D., Burch, D., Marshall, A., and Naylor, S.L. (1988) Restriction fragment length polymorphism studies show consistent loss of chromosome 3p alleles in small cell lung cancer patient’s tumors. J. Clin. Invest. 82:502–507.

    Article  PubMed  CAS  Google Scholar 

  41. Morita, R., Siegfried, J.M., Resau, J., Keler, S.M., Zhou, J., and Testa, J.R. (1990) Chromosome alterations in 21 non-small cell lung carcinomas. Genes Chrom. Cancer 2:328–338.

    Google Scholar 

  42. Fleijter, W.L., Li, F.F., Antman, K.H., and Testa, J.R. (1989) Recurring loss involving chromosomes 1, 3 and 22 in malignant mesothelioma. Genes Chrom. Cancer 1:148–154.

    Google Scholar 

  43. Miller, Y.E., Drabkin, H.A., Jones, C., and Fisher, J.H. (1990) Human aminoacylase1: cloning, regional assignment to distal chromosome 3p21.1, and identification of a crosshybridizing sequence on chromosome 18. Genomics 8:149–154.

    Article  PubMed  CAS  Google Scholar 

  44. Ginzinger, D.G., Shridhar, V., Baldini, A., Taggart, R.T., Miller, O.J., and Smith, D.I. (1992) The human loci DNF15S2 and D3S94 have a high degree of sequence similarity to acyl-peptide hydrolase and are located at 3p21.3. Am. J. Hum. Genet. 50:826–833.

    PubMed  CAS  Google Scholar 

  45. Sparkes, R.S., Sparkes, M.C., Wilson, M.G., et al. (1980) Regional assignmentof genes for human esterase D and retinoblastoma to chromosome band 13g14. Science208:1042–1043.

    Google Scholar 

  46. Lee, W.H., Bookstein, R., Hong, F., et al. (1987) The retinoblastoma susceptibility gene: cloning, identification, and sequence. Science 253:1394–1399.

    Article  Google Scholar 

  47. Bird, A.P.,Taggart, M., Frommer, M., Miller, O.J., and MacLeod, D. (1985) A fraction of the mouse genome that is derived from islands of nonmethlylated CpGrich DNA. Cell 40:9199.

    Article  Google Scholar 

  48. Bird, A.P. (1986) CpG-rich islands and the function of DNA methylation. Nature 321:209–213.

    Article  PubMed  CAS  Google Scholar 

  49. Lindsay, S., and Bird, A.P. (1987) Use of restriction enzymes to detect potential gene sequences in mammalian DNA. Nature 327:336–338.

    Google Scholar 

  50. Golembieski, W.A., Smith, S.E., Recchia, F., et al. (1989) Isolation of large numbers of chromosome 3-specific cosmids containing clusters of rare restriction-endonuclease sites. Am. J. Hum. Genet. 49:581–589.

    Google Scholar 

  51. Smith, D.I., Golembieski, W., Drabkin, H.A., and Kiousis, S. (1989) Identification of two cosmids derived from within chromosomal band 3p21.1 that contain clusters of rare restriction sits and evolutionarily conserved sequences. Am. J. Hum. Genet. 45:443–447.

    PubMed  CAS  Google Scholar 

  52. Gemmill, R.M., Varella-Garcia, M.V., Smith, D.I., et al. (1991) A 2.5 Mb physical map within 3p21.1 spans the breakpoint associated with Greig Cephalopolysyndactyly syndrome. Genomics 11:93–102.

    Article  PubMed  CAS  Google Scholar 

  53. Verkerk, A.H.M.H., Pieretti, M., Sutcliffe, J.S., et al. (1991) Identification of a gene (FMR 1) containing a CCG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65:905–914.

    Article  PubMed  CAS  Google Scholar 

  54. Brook, J.D., McCurrach, M.E., Harley, H.G., et al. (1992) Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeatat the 3’ end of a transcript encoding a protein kinase family member. Cell 68:799–808.

    Article  PubMed  CAS  Google Scholar 

  55. The Huntington’s Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72:971–983.

    Article  Google Scholar 

  56. Otita, M., Suzuki, Y., Sekiya, T., and Hayashi, K. (1989) Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics 5:874–879.

    Article  Google Scholar 

  57. Daly, M.C., Hensel, C.H., Xiang, R.-H., et al. (1993). Characterization of a homozygous deletion in the small cell lung cancer cell lie, NCI H740. Am. J. Hum. Genet. 53:A290.

    Google Scholar 

  58. Yamakawa, K., Murata, Y., Tamari, M., et al. (1993) Identification and characterization of a 9 Kb somatic homozygous deletion at 3p21.3-p22 in a lung cancer cell line. Amer. J. Hum. Genet. 53:A390.

    Google Scholar 

  59. Berger, R., Bloomfield, C.D., and Sutherland, G.R. (1985) Human Gene Mapping 8: Report of the committee on chromosome rearrangements in neoplasia and on fragile sites. Cytogenet. Cell Genet. 40:490–535.

    Article  CAS  Google Scholar 

  60. Glover, T.W., Berger, C., Coyle, J., and Echo, B. (1984) DNA polymerase alpha inhibition by aphidicolin induces gaps and breaks at common fragilesites in human chromosomes. Hum. Genet. 67:136–142.

    CAS  Google Scholar 

  61. Daly, M.C., Douglas, J.B., Bleehen, N.M., et al. (1991) An unusually proximal deletion on the short arm ofchromosome 3 in a patient with small cell lung cancer. Genomics 9:113–119.

    Article  PubMed  CAS  Google Scholar 

  62. Yokoyama, S., Yamakawa, K., Tsuchiya, E., Murata, M, Sakiyama, S., and Nakamura, Y. (1992) Deletion mapping on the short arm of chromosome 3 in squamous cell carcinoma and adenocarinoma of the lung. Cancer Res. 52:873877.

    Google Scholar 

  63. Drabkin, H.A., Bradley, C., Hart, I., Bleskan, J., Li, F.P., and Patterson, D. (1985) Translocation of c-myc in the hereditary renal cell carcinoma associated with a t(3;8)(p14.2;g24.13) chromosomal translocation. Proc. Natl. Acad. Sci. USA 82:6980–6984.

    Article  PubMed  CAS  Google Scholar 

  64. Hecht, F., and Sutherland, G.R. (1984) Fragile sites and cancer breakpoints. Cancer Genet. Cytogenet. 12:179–181.

    Article  CAS  Google Scholar 

  65. Hecht, F., and Glover, T.W. (1984) Cancer chromosome breakpoints and common fragile sites induced by aphidicolin. Cancer Genet. Cytogenet. 13:185–188.

    CAS  Google Scholar 

  66. Bardenheuer, W., Szymanski, S., Lux, A., et al. (1994) Characterization of a microdissection library from human chromosome region 3p 14. Genomics 19:291–302.

    Article  PubMed  CAS  Google Scholar 

  67. Boldog, F.L., Gemmill, R.M., Wilke, C.M., et al. (1993) Positional cloning of the hereditary renal carcinoma 3;8 chromosome translocation breakpoint. Proc. Natl. Acad. Sci. USA 90:8509–8513.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Internal Medicine, USA

    David I. Smith Ph.D.

  2. Department of Molecular Biology and Genetics, Wayne State University School of Medicine, Detroit, Michigan, USA

    Wanguo Liu Ph.D. & William Paradee B.S.

Authors
  1. David I. Smith Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wanguo Liu Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Viji Shridhar M.S.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William Paradee B.S.
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer-Verlag New York Inc.

About this paper

Cite this paper

Smith, D.I., Liu, W., Shridhar, V., Paradee, W. (1995). The Cloning of Tumor Suppressor Genes from the Short Arm of Human Chromosome 3 that Play a Role in the Development of Renal Cell Carcinoma. In: Biology of Renal Cell Carcinoma. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-2536-2_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-2536-2_5

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-7571-8

  • Online ISBN: 978-1-4612-2536-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation