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Nonrandom chromosome losses in tumorigenic revertants of hybrids between isogeneic immortal and neoplastic human uroepithelial cells

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Somatic Cell and Molecular Genetics

Abstract

Somatic cell hybrid analysis was used to examine the role of recessive cancer genes in tumorigenic transformation in vitro of human uroepithelial cells (HUC). Hybrids between nontumorigenic pseudodiploid SV40-immortalized HUC (SV-HUC) and two aggressive grade III transitional cell carcinomas (TCC) produced in nude mice after in vitro exposure of SV-HUC to 3-methylcholanthrene (MC) were completely suppressed for tumorigenicity at early passage. Tumorigenic reversion occurred after five or more passages in culture and was always accompanied by chromosome losses. Overall, the tumorigenic revertants showed statistically significant losses of chromosomes 1, 4, 5, 9q, 12, 14q, and 17 (all P≤0.05) as compared to losses in suppressed hybrids. In addition, hybrid reversion was accompanied by losses that left specific tumors with a single remaining homolog of certain chromosomes (i.e., 3, 5q, 11p, 17p, and 18q). These losses were also considered significant because of the likelihood that genes on these chromosomes were reduced to homozygosity. Many of the significant losses (i.e., 5q, 9q, 11p, and 17p) were of chromosomes that are frequently lost in clinical TCC. Thus, these results support the hypothesis that these chromosomes contain genes whose loss leads to HUC tumorigenesis.

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Literature cited

  1. Fearon, E.R., and Vogelstein, B. (1990).Cell 61759–767.

    Google Scholar 

  2. Sandberg, A.A. (1990).The Chromosomes in Human Cancer and Leukemia (Elsevier, New York), pp. 789–924.

    Google Scholar 

  3. Tsai, Y.C., Nichols, P.W., Hiti, A.L., Williams, Z., Skinner, D.G., and Jones, P.A. (1990).Cancer Res. 5044–47.

    Google Scholar 

  4. Stanbridge, E.J. (1988).Cancer Surv. 7317–324.

    Google Scholar 

  5. Huang, H.J.S., Yee, J.K., Shew, J.Y., Chen, P.L., Bookstein, R., Friedmann, T., Lee, E.Y.H.P., and Lee, W.H. (1988).Science 2421563–1566.

    Google Scholar 

  6. Baker, S.J., Markowitz, S., Fearon, E.R., Willson, J.K.V., and Vogelstein, B. (1990).Science 249912–915.

    Google Scholar 

  7. Harris, H., Miller, O., Klein, G., Worst, P., and Tachibana, S. (1969).Nature 223363–368.

    Google Scholar 

  8. Stanbridge, E.J., Der, C.J., and Doerson, C.J. (1982).Science 215252–259.

    Google Scholar 

  9. Knudson, A. (1985).Cancer Res. 451437–1443.

    Google Scholar 

  10. Kaelbling, M., and Klinger, H.P. (1986).Cytogenet. Cell Genet. 4165–70.

    Google Scholar 

  11. Benedict, W.F., Weissman, B.E., Mark, C., and Stanbridge, E.J. (1984).Cancer Res. 443471–3479.

    Google Scholar 

  12. Stanbridge, E.J., Flandermeyer, R.R., Daniels, D.W., and Nelson-Rees, W.A. (1981).Somat. Cell Genet. 7699–712.

    Google Scholar 

  13. Krizman, D.B., Giovanella, B.C., and Tainsky, M.A. (1990).Somat. Cell Mol. Genet. 1615–27.

    Google Scholar 

  14. Cairns, J. (1975).Nature 255197–200.

    Google Scholar 

  15. Kaighn, M.E., Gabrielson, E.W., Iman, D.S., Pauls, E.A., and Harris, C.C. (1990).Cancer Res. 501890–1896.

    Google Scholar 

  16. Zajchowski, D.A., Band, V., Trask, D.K., Kling, D., Connolly, J.L., and Sager, R. (1990).Proc. Natl. Acad. Sci. U.S.A. 872314–2318.

    Google Scholar 

  17. Johnson, T.L., and Moyer, M.P. (1990).In Vitro Cell Dev. Biol. 261095–1100.

    Google Scholar 

  18. Pereira-Smith, O.M., and Smith, J.R. (1988).Proc. Natl. Acad. Sci. U.S.A. 856042–6046.

    Google Scholar 

  19. Christian, B.J., Loretz, L.J., Oberley, T.D., and Reznikoff, C.A. (1987).Cancer Res. 476066–6073.

    Google Scholar 

  20. Meisner, L.F., Wu, S.Q., Christian, B.J., and Reznikoff, C.A. (1988).Cancer Res. 483215–3220.

    Google Scholar 

  21. Reznikoff, C.A., Loretz, L.J., Christian, B.J., Wu, S.Q., and Meisner, L.F. (1988).Carcinogenesis 91427–1436.

    Google Scholar 

  22. Wu, S.Q., Christian, B.J., Reznikoff, C.A., and Meisner, L.F. (1988).Cancer Genet. Cytogenet. 3677–87.

    Google Scholar 

  23. Christian, B.J., Kao, C., Wu, S.Q., Meisner, L.F., and Reznikoff, C.A. (1990).Cancer Res. 504779–4786.

    Google Scholar 

  24. Wu, S.Q., Storer, B.E., Bookland, E.A., Klingelhutz, A.J., Gilchrist, K.W., Meisner, L.F., Oyasu, R., and Reznikoff, C.A. (1991).Cancer Res. 513323–3326.

    Google Scholar 

  25. Klingelhutz, A.J., Wu, S.Q., Bookland, E.A., and Reznikoff, C.A. (1991).Genes, Chromo. Cancer 3346–357.

    Google Scholar 

  26. Southern, P.J., and Berg, P. (1982).J. Mol. Appl. Genet. 1327–341.

    Google Scholar 

  27. Brash, D.E., Reddel, R.R., Quanrud, M., Yang, K., Farrell, M.P., and Harris, C.C. (1987).Mol. Cell Biol. 52031–2034.

    Google Scholar 

  28. Jacobs, L., and DeMars, R. (1977).Handbook of Mutagenicity Test Procedures (eds.) Kilby, B.J., Legator, M., Nichols, W., and Ramlet, C. (Elsevier/North-Holland Biomedical Press, New York), pp. 193–220.

    Google Scholar 

  29. Szybalska, E., and Szybalski, W. (1962).Proc. Natl. Acad. Sci. U.S.A. 482026–2034.

    Google Scholar 

  30. Mulligan, R.C., and Berg, P. (1987).Proc. Natl. Acad. Sci. U.S.A. 782072–2076.

    Google Scholar 

  31. Davidson, R.L., and Gerald, P.S. (1976).Somat. Cell Genet. 2165–176.

    Google Scholar 

  32. Reznikoff, C.A., Gilchrist, K.W., Norback, D.H., Cummings, K.B., Ertürk, E., and Bryan, G.T. (1983).Am. J. Pathol. 111263–272.

    Google Scholar 

  33. Lehman, E.C. (1975).Statistical Methods Based on Ranks (Holden-Day, San Francisco) Chapter 1, pp. 1–54.

    Google Scholar 

  34. Atkin, N.B., and Baker, M.C. (1985).Cancer Genet. Cytogenet. 15253–268.

    Google Scholar 

  35. Sandberg, A.A. (1986).Cancer Genet. Cytogenet. 19163–175.

    Google Scholar 

  36. Gibas, Z., Prout, G.R., Jr., Connolly, J.G., Pontes, J.E., and Sandberg, A.A. (1984).Cancer Res. 441257–1264.

    Google Scholar 

  37. Smeets, W., Pauwels, R., Laarakkers, L., Debruyn, F., and Geraedts, J. (1987).Cancer Genet. Cytogenet. 2929–41.

    Google Scholar 

  38. Babu, V.R., Lutz, M.D., Miles, B.J., Farah, R.N., Weiss, L., and Van Dyke, D.L. (1987).Cancer Res. 476800–6805.

    Google Scholar 

  39. Atkin, N.B., and Fox, M.F. (1990).Cancer Genet. Cytogenet. 46129–131.

    Google Scholar 

  40. Fearon, E.R., Feinberg, A.P., Hamilton, S.H., and Vogelstein, B. (1985).Nature 318377–380.

    Google Scholar 

  41. Olumi, A.F., Tsai, Y.C., Nichols, P.W., Skinner, D.G., Cain, D.R., Bender, L.I., and Jones, P.A. (1990).Cancer Res. 507081–7083.

    Google Scholar 

  42. Hopman, A.H., Poddighe, P.J., Smeets, A.W.G.B., Moesker, O., Beck, J.L.M., Vooijs, G.P., and Ramaekers, F.C.S. (1989).Am. J. Pathol. 1351105–1117.

    Google Scholar 

  43. Presti, J.C., Reuter, V.E., Galan, T., Fair, W.R., and Cordon-Cardo, C. (1991).Cancer Res. 515405–5409.

    Google Scholar 

  44. Mikkelsen, R., and Cavenee, W.K. (1990).Cell Growth Differentiation 1202–207.

    Google Scholar 

  45. Zingg, E.J. (1985).Bladder Cancer (Springer-Verlag, New York) p. 26.

    Google Scholar 

  46. Vogelstein, B., Fearon, E.R., Kern, S.E., Hamilton, S.R., Preisinger, A.C., Namkamura, Y., and White, R. (1989).Science 244207–211.

    Google Scholar 

  47. Kinzler, K.W., Nilbert, M.C., Vogelstein, B., Bryan, T.M., Levy, D.B., Smith, K.J., Preisinger, A.C., Hamilton, S.R., Hedge, P., Markham, A., Carlson, M., Joslyn, G., Groden, J., White, R., Miki, Y., Miyoshi, Y., Nishisho, I., and Nakamura, Y. (1990).Science 2511366–1370.

    Google Scholar 

  48. Call, K.M., Glaser, T., Ito, C.Y., Buckler, A.J., Pelletier, J., Haber, D.A., Rose, E.A., Kral, A., Yeger, H., Lewis, W.H., Jones, C., and Houseman, D.E. (1990).Cell 60509–520.

    Google Scholar 

  49. Baker, S.J., Fearon, E.R., Nigro, J.M., Hamilton, S.R., Preisinger, A.C., Milburn Jessup, J., VanTuinen, P., Ledbetter, D.H., Barker, D.F., Nakamura, Y., White, R., and Vogelstein, B. (1989).Science 244217–219.

    Google Scholar 

  50. Fearon, E.R., Cho, K.R., Nigro, J.M., Kern, S.E., Simons, J.W., Ruppert, J.M., Hamilton, S.R., Preisinger, A.C., Thomas, G., Kinzler, K.W., and Vogelstein, B. (1990).Science 24749–56.

    Google Scholar 

  51. LaForgia, S., Morse, B., Levy, J., Barnea, G., Cannizzaro, L.A., Li, F., Nowell, P.C., Boghosian-Sell, L., Glick, J., Weston, A., Harris, C.C., Drabkin, H., Patterson, D., Croce, C.M., Schlessinger, J., and Huebner, K. (1991).Proc. Natl. Acad. Sci. U.S.A. 885036–5040.

    Google Scholar 

  52. Sidransky, D., Von Eshenbach, A., Tsai, Y.C., Jones, P., Summerhayes, I., Marshall, F., Paul, M., Green, P., Hamilton, S.R., Frost, P., and Vogelstein, B. (1991).Science 252706–709.

    Google Scholar 

  53. Horowitz, J.M., Park, S.H., Bogenmann, E., Cheng, J.C., Yandell, D.W., Kaye, F.J., Minna, J.D., Dryja, T.P., and Weinberg, R.A. (1990).Proc. Natl. Acad. Sci. U.S.A. 872775–2779.

    Google Scholar 

  54. Schreier, A.A., and Gruber, J. (1990).J. Natl. Cancer Inst. 82354–360.

    Google Scholar 

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Klingelhutz, A.J., Wu, SQ. & Reznikoff, C.A. Nonrandom chromosome losses in tumorigenic revertants of hybrids between isogeneic immortal and neoplastic human uroepithelial cells. Somat Cell Mol Genet 17, 551–565 (1991). https://doi.org/10.1007/BF01233620

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