Are Activated Proto-ONC Genes Cancer Genes?

  • Peter H. Duesberg
  • Michael Nunn
  • Nancy Kan
  • Dennis Watson
  • Peter H. Seeburg
  • Takis Papas
Part of the NATO ASI Series book series (NSSA, volume 91)


Cellular genes, which are related to retroviral transforming (onc) genes have, therefore, been termed proto-onc genes, are now widely believed to be potential cancer genes. In some tumors, proto-onc genes are mutated or expressed more than in normal cells. Under these conditions, proto-onc genes are thought to be activated to function as cancer genes in view of two hypotheses: The one geneone cancer hypothesis which suggests that one activated proto-onc gene, like a viral onc gene, is sufficient to cause cancer and the multigene-one cancer hypothesis which speculates that an activated proto-onc gene, unlike a viral onc gene, is a necessary but not a sufficient cause of cancer. The evidence for these hypotheses is reviewed here using as examples proto-myc and proto-ras, the cellular prototypes of the onc genes of avian carcinoma virus MC29 and murine Harvey sarcoma virus. Since mutated or transcriptionally activated proto-onc genes are not consistently associated with a specific tumor and do not transform primary cells and since as yet no set of an activated proto-onc gene and a complementary cancer gene with transforming function has been isolated from a tumor, there is no proof that activated proto-onc genes are sufficient or even necessary to cause cancer.


Cancer Genes Burkitt Lymphoma Transforming Gene Rous Sarcoma Virus Helper Gene 
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  1. 1).
    ROUS, P. (1967). The challenge to man of the neoplastic cell. Science, 157, 24.CrossRefGoogle Scholar
  2. la).
    BERENBLUM, I. (1981). Sequential aspects of chemical carcinogenesis: Skin. In: “Cancer, Vol. 1”, F. Becker, ed., Plenum Press, New York.Google Scholar
  3. 2).
    KNUDSON, A.G. Genetic influences in human tumors, ibid. Google Scholar
  4. 3).
    FOULDS, L. (1969). “Neoplastic Development, Vol. I & II”, Academic Press, New York.Google Scholar
  5. 4).
    COOPER, G.M. (1982). Cellular transforming genes, Science, 218, 801.CrossRefGoogle Scholar
  6. 5).
    DUESBERG, P.H. (1983). Retroviral transforming genes in normal cells?, Nature, 304, 219.CrossRefGoogle Scholar
  7. 6).
    HELDIN, C.-H. & WESTERMARK, B. (1984). Growth factors: Mechanism of action and relation to oncogenes, Cell, 37, 9.CrossRefGoogle Scholar
  8. 7).
    PETERSON, T.A., YOCHEM, J., BYERS, B., NUNN, M.F., DUESBERG, P.H., DOOLITTLE, R.F. & REED, S.E. (1984). A relationship between the yeast cell cycle genes CDC4 and CDC36 and the ets sequence of oncogenic virus E26, Nature, 309, 556.CrossRefGoogle Scholar
  9. 8).
    MARTIN, G.S. (1970). Rous sarcoma virus: A function required for the maintenance of the transformed state, Nature,221, 1021.CrossRefGoogle Scholar
  10. 9).
    SHIH, T.Y., WEEKS, M.O., YOUNG, M.A. & SCOLNICK, E.M. (1979). p21 of Kirsten murine sarcoma virus is thermolabile in a viral mutant temperature sensitive for the maintenance of transformation, J. Virol., 31, 546.Google Scholar
  11. 10).
    PAWSON, A., GUYDEN, J., KUNG, T.-H., RADKE, K., GILMORE, T. & MARTIN, G.S. (1980). A strain of Fujinami sarcoma virus which is temperature-sensitive in protein phosphorylation and cellular transformation, Cell, 22, 767.CrossRefGoogle Scholar
  12. 11).
    LEE, W.-H., BISTER, K., MOSCOVICI, C. & DUESBERG, P.H. (1981). Temperature-sensitive mutants of Fujinami sarcoma virus: Tumorigenicity and reversible phosphorylation of the transforming p140 protein, J. Viral., 38, 1064.Google Scholar
  13. 12).
    PALMIERI, S., BEUG, H. & GRAF, T. (1982). Isolation and characterization of four new temperature-sensitive mutants of avian erythroblastosis virus (AEV), Virology, 123, 296.CrossRefGoogle Scholar
  14. 13).
    DUESBERG, P.H. & VOGT, P.K. (1970). Differences between the ribonucleic acids of transforming and nontransforming avian tumor viruses, Proc. Natl. Acad. Sci. USA, 67, 1673.CrossRefGoogle Scholar
  15. 14).
    MARTIN, G.S. & DUESBERG, P.H. (1972). The a-subunit in the RNA of transforming avian tumor viruses: I. Occurrence in different virus strains. II. Spontaneous loss resulting in nontransforming variants, Virology, 47, 494.CrossRefGoogle Scholar
  16. 15).
    WEI, C.-M., LOWY, D.R. & SCOLNICK, E.M. (1980). Mapping of transforming region of the Harvey murine sarcoma virus genome by using insertion-deletion mutants constructed in vitro,Proc. Natl. Acad. Sci. USA, 77, 4674.CrossRefGoogle Scholar
  17. 16).
    GOFF, S.P. & BALTIMORE, D. (1982). The cellular oncogene of the Abelson murine leukemia virus genome. In: “Advances in Viral Oncology, Volume 1”, G. Klein, ed., Raven Press, New York.Google Scholar
  18. 17).
    SRINIVASAN, A., DUNN, C.Y., YUASA, Y., DEVARE, S.G., REDDY, E.P. & AARONSON, S.A. (1982). Abelson murine leukemia virus: Structural requirements for transforming gene function, Proc. Natl. Acad. Sci. USA, 79, 5508.CrossRefGoogle Scholar
  19. 18).
    EVANS, L.H. & DUESBERG, P.H. (1982). Isolation of a transformation-defective deletion mutant of Moloney murine sarcoma virus, J. Virol., 41, 735.Google Scholar
  20. 19).
    DUESBERG, P.H., PHARES, W. & LEE, W.H. (1983). The low tumori-genic potential pf PRCII, among viruses of the Fujinami sarcoma virus subgroup, corresponds to an internal fps deletion of the transforming gene, Virology, 131, 144.CrossRefGoogle Scholar
  21. 20).
    DUESBERG, P.H. (1980). Transforming genes of retroviruses, Cold Spring Harbor Symp. Quant. Biol., 44, 13.CrossRefGoogle Scholar
  22. 21).
    MELLON, P., PAWSON, A., BISTER, K., MARTIN, G.S. & DUESBERG, P.H. (1978). Specific RNA sequences and gene products of MC29 avian acute leukemia virus, Proc. Natl. Acad. Sci. USA, 75, 5874.CrossRefGoogle Scholar
  23. 22).
    ROBINS, T., BISTER, K., GARON, C., PAPAS, T. & DUESBERG, P.H. (1982). Structural relationship between a normal chicken DNA locus and the transforming gene of the avian acute leukemia virus MC29, J. Virol., 41, 635.Google Scholar
  24. 23).
    DUESBERG, P.H., BISTER, K. & VOGT, P.K. (1977). The RNA of avian acute leukemia virus MC29, Proc. Natl. Acad. Sci. USA, 74, 4320.CrossRefGoogle Scholar
  25. 24).
    BISTER, K. & DUESBERG, P.H. (1982). Genetic structure and transforming genes of avian retroviruses. In: “Advances in Viral Oncology, Volume 1”, G. Klein, ed., Raven Press, New York.Google Scholar
  26. 25).
    PAPAS, T.S., KAN, N.K., WATSON, D.K., FLORDELLIS, C.S., PSALLIDOPOULOS, M.C., LAUTENBERGER, J., SAMUEL, K.P. & DUESBERG, P.H. (1982). myc-related genes in viruses and cells. In: “Cancer Cells 2/Oncogenes and Viral Genes”, G.F. Wande Woude, A.J. Levine, W.C. Topp & J.D. Watson, eds., Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.Google Scholar
  27. 26).
    WATSON, D.K., REDDY, E.P., DUESBERG, P.H., PAPAS, T.S. (1983). Nucleotide sequence analysis of the chicken c-myc gene reveals homologous and unique coding regions by comparison with the transforming gene of avian myelocytomatosis virus MC29 4gagmyc, Proc. Natl. Acad. Sci. USA, 80, 2146.CrossRefGoogle Scholar
  28. 27).
    SHIH, C.-K., LINIAL, M., GOODENOW, M.M. & HAYWARD, W.S. (1984). Nucleotide sequence 5’ of the chicken c-myc coding region: Localization of a noncoding exon that is absent from myc transcripts in most avian leukosis virus-induced lymphomas, Proc. Natl. Acad. Sci. USA, 81, 4697.CrossRefGoogle Scholar
  29. 28).
    KAN, N.C., FLORDELLIS, C.S., MARK, G.E., DUESBERG, P.H. & PAPAS, T.S. (1984). Nucleotide sequence of avian carcinoma virus MH2: Two potential onc genes, one related to avian virus MC29, the other to murine sarcoma virus 3611, Proc. Nati. Acad. Sci. USA, 81, 3000.CrossRefGoogle Scholar
  30. 29).
    KAN, N.C., FLORDELLIS, C.S., MARK, G.E., DUESBERG, P.H. & PAPAS, T.S. (1984). A common onc gene sequence transduced by avian carcinoma virus MH2 and by murine sarcoma virus 3611, Science, 223, 813.CrossRefGoogle Scholar
  31. 30).
    SCHWARTZ, D.E., TIZARD, R. & GILBERT, W. (1983). Nucleotide sequence of Rous sarcoma virus, Cell, 32, 853.CrossRefGoogle Scholar
  32. 31).
    PACHL, C., BIEGALKE, B. & LINIAL, M. (1983). RNA and protein encoded by MH2 virus: Evidence for subgenomic expression of V-myc, J. Virol. 45, 133.Google Scholar
  33. 32).
    HANN, S.R., ABRAMS, H.D., ROHRSCHNEIDER, L.R. & EISENMAN, R.N. (1983). Proteins encoded by v-myc and c-myc oncogenes: Identification and localization in acute leukemia virus transformants and bursal lymphoma in cell lines, Cell, 34, 781.CrossRefGoogle Scholar
  34. 33).
    ALITALO, K., RAMSAY, G., BISHOP, J.M., PFEIFFER, S.O., COLBY, W.W. & LEVINSON, A.D. (1983). Identification of nuclear proteins encoded by viral and cellular myc oncogenes, Nature, 306, 274.CrossRefGoogle Scholar
  35. 34).
    CHISWELL, D.J., RAMSEY, G. & HAYMAN, M.J. (1981). Two virus-specific RNA species are present in cells transformed by defective leukemia virus OK10, J. Virol., 40, 301.Google Scholar
  36. 35).
    LEVY, L.S., GARDNER, M.B. & CASEY, J.W. (1984). Isolation of a feline leukaemia provirus containing the oncogene myc from a feline lymphosarcoma, Nature, 308, 853.CrossRefGoogle Scholar
  37. 36).
    SEEBURG, P.H., LEE, W.-H., NUNN, M.F. & DUESBERG, P.H. (1984). The 5’ end of the transforming gene of Fujinami sarcoma virus and of the cellular proto-fps gene are not colinear, Virology, 133, 460.CrossRefGoogle Scholar
  38. 37).
    LEE, W.-H., PHARES, W. & DUESBERG, P.H. (1983). Structural relationship between chicken DNA locus, proto-fps, and the transforming gene of Fujinami sarcoma virus (Agag-fps),Virology, 129, 79.CrossRefGoogle Scholar
  39. 38).
    RUSHLOW, K.E., LAUTENBERGER, J.A., PAPAS, T.S., BALUDA, M.A., PERBAL, B., CHIRIKJIAN, J.G. & REDDY, E.P. (1982). Nucleotide sequence of the transforming gene of avian myeloblastosis virus, Science, 216, 1421.CrossRefGoogle Scholar
  40. 39).
    KLEMPNAUER, K.-H., GONDA, T.S. & BISHOP, J.M. (1982). Nucleotide sequence of the retroviral leukemia gene v-myb and its progeintor c-myb: The architecture of a transduced oncogene, Cell, 31, 453.CrossRefGoogle Scholar
  41. 40).
    NUNN, M.F., SEEBURG, P.H., MOSCOVICI, C. & DUESBERG, P.H. (1983). Tripartite structure of the avian erythroblastosis virus E26 transforming gene, Nature, 306, 391.CrossRefGoogle Scholar
  42. 41).
    NUNN, M., WEIHER, H., BULLOCK, P. & DUESBERG, P.H. (1984). Avian erythroblastosis virus E26: Nucleotide sequence of the tripartite one gene and of the LTR, and analysis of the cellular prototype of the viral ets sequence, Virology, 139, 330.CrossRefGoogle Scholar
  43. 42).
    TAKEYA, T. & HANAFUSA, H. (1983). Structure and sequence of the cellular gene homologous to the src gene of RSV and the mechanism of the generation of the viral transforming gene, Cell, 32, 881.CrossRefGoogle Scholar
  44. 43).
    CAMPISI, J., GRAY, H.E., PARDEE, A.B., DEAN, M. & SONENSHEIN, G.E. (1984). Cell-cycle control of c-myc but not c-ras expression is lost following chemical transformation, Cell, 36, 241.CrossRefGoogle Scholar
  45. 44).
    TAKEYA, T. & HANAFUSA, H. (1982). DNA sequence of the viral and cellular src gene of chickens II. Comparison of the src genes of two strains of avian sarcoma virus and of the cellular homolog, J. Virol., 44, 12.Google Scholar
  46. 45).
    PARKER, R.C., VARMUS, H.E. & BISHOP, J.M. (1984). Expression of v-src and chicken c-src in rat cells demonstrates qualitative differences between pp60v-src and pp60c-src, Cell, 37, 131.CrossRefGoogle Scholar
  47. 46).
    PARSONS, J.T., BRYANT, D., WILKERSON, V., GILMARTIN, G. & PARSONS, S.J. (1984). Site-directed mutagenesisofRous sarcoma virus pp6Osrc: Identification of functional domains required for transformation. In: “Cancer Cells 2/Oncogenes and Viral Genes”, G.F. Vande Woude, A.J. Levine, W.C. Topp & J.D. Watson, eds., Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.Google Scholar
  48. 47).
    SHALLOWAY, D., COUSSENS, P.M. & YACIUK, P. (1984). c-src and src homolog overexpression in mouse cells, ibid. Google Scholar
  49. 48).
    MILLER, A.D., CURRAN, T. & VERMA, I.M. (1984). c-fos protein can induce cellular transformation: A novel mechanism of activation of a cellular oncogene, Cell, 36, 51.CrossRefGoogle Scholar
  50. 49).
    SODROSKI, J.G., GOH, W.C. & HASELTINE, W.A. (1984). Transforming potential of a human protooncogene (c-fps/fes) locus, Proc. Natl. Acad. Sci. USA, 81, 3039.CrossRefGoogle Scholar
  51. 50).
    IBA, H., TAKEYA, T., CROSS, F.R., HANAFUSA, T. & HANAFUSA, H. (1984). Rous sarcoma virus variants that carry the cellular src gene instead of the viral src gene cannot transform chicken embryo fibroblasts, Proc. Nati. Acad. Sci. USA, 81, 4424.CrossRefGoogle Scholar
  52. 51).
    WILHELMSEN, K.C., TARPLEY, W.G. & TEMIN, H.M. (1984). Identification of some of the parameters governing transformation by oncogenes in retroviruses. In: “Cancer Cells 2/Oncogenes and Viral Genes”, G.F. Wande Woude, A.J. Levine, W.C. Topp & J.D. Watson, eds., Cold Spring Harbor Laboratory, Cold Spring Harbor, New YorkGoogle Scholar
  53. 52).
    BLAIR, D.G., OSKARSSON, M., WOOD, T.G., MCCLEMENTS, W.C., FISCHINGER, P.J. & VANDE WOUDE, G.F. (1981). Activation of the transforming potential of a normal cell sequence: A molecular model for oncogenesis, Science, 212, 941.CrossRefGoogle Scholar
  54. 53).
    CHANG, E.H., FURTH, M.E., SCOLNICK, E.M. & LOWY, D.R. (1982). Tumorigenic transformation of mammalian cells induced by a normal human gene homologous to the oncogene of Harvey murine sarcoma virus, Nature, 297, 479.CrossRefGoogle Scholar
  55. 54).
    LAND, H., PARADA, L.F. & WEINBERG, R.A., (1983). Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes, Nature, 304, 596.CrossRefGoogle Scholar
  56. 55).
    LAND, H., PARADA, L.F. & WEINBERG, R.A. (1983). Cellular oncogenes and multistep carcinogenesis, Science, 222, 771.CrossRefGoogle Scholar
  57. 56).
    GROSS, L. (1970). “Oncogenic Viruses”, Pergamon Press, New York.Google Scholar
  58. 57).
    TOOZE, J., ed. (1973). “The Molecular Biology of Tumour Viruses”, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.Google Scholar
  59. 58).
    WEISS, R.A., TEICH, N.M., VARMUS, H. & COFFIN, J.M., eds., (1982). “Molecular Biology of Tumor Viruses: RNA Tumor Viruses, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.Google Scholar
  60. 59).
    HUEBNER, R.J. & TODARO, G.J. (1969). Oncogenes of RNA tumor viruses as determinants of cancer, Proc. Natl. Acad. Sci. USA, 64, 1087.CrossRefGoogle Scholar
  61. 60).
    BISHOP, J.M., COURTNEIDGE, S.A., LEVINSON, A.D., OPPERMANN, H., QUINTRELL, N., SHEINESS, D.K., WEISS, S.R. & VARMUS, H.E. (1980). Origin and function of avian retrovirus transforming genes, Cold Spring Harbor Symp. Quant. Biol., 44, 919.CrossRefGoogle Scholar
  62. 61).
    BISHOP, J.M. (1981). Enemies within: The genesis of retrovirus oncogenes, Cell, 23, 5.CrossRefGoogle Scholar
  63. 62).
    WANG, L.-H., SNYDER, P., HANAFUSA, T., MOSCOVICI, C. & HANAFUSA, H. (1980). Comparative analysis of cellular and viral sequences related to sarcomagenic cell transformation, Cold Spring Harbor Symp. Quant. Biol., 44, 766.CrossRefGoogle Scholar
  64. 63).
    KARESS, R.E., HAYWARD, W.S. & HANAFUSA, H. (1980). Transforming proteins encoded by the cellular information of recovered avian sarcoma viruses, Cold Spring Harbor Symp. Quant. Biol., 44, 765.CrossRefGoogle Scholar
  65. 64).
    HAYWARD, W.S., NEEL, B.G. & ASTRIN, S.M. (1981). Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis, Nature, 290, 475.CrossRefGoogle Scholar
  66. 65).
    KLEIN, G. (1981). The role of gene dosage and genetic transpositions in carcinogenesis, Nature, 294, 313.CrossRefGoogle Scholar
  67. 66).
    TABIN, C.J., BRADLEY, S.M., BARGMANN, C.I., WEINBERG, R.A., PAPAGEORGE, A.G., SCOLNICK, E.M., DHAR, R., LOWY, D.R. & CHANG, E.H. (1982). Mechanism of activation of a human oncogene, Nature, 300, 143.CrossRefGoogle Scholar
  68. 67).
    COOPER, G.M. & NEIMAN, P.E. (1981). Two distinct candidate transforming genes of lymphoid leukosis virus-induced neoplasms, Nature, 292, 857.CrossRefGoogle Scholar
  69. 68).
    DIAMOND, A., COOPER, G.M., RITZ, J. & LANE, M.-A. (1983). Identification and molecular cloning of the human BZym transforming gene activated in Burkitt’s lymphomas, Nature, 305, 112.CrossRefGoogle Scholar
  70. 69).
    RULEY, H.E. (1983). Adenovirus early region lA enables viral and cellular transforming genes to transform primary cells in culture, Nature, 304, 602.CrossRefGoogle Scholar
  71. 70).
    LEDER, P., BATTEY, J., LENOIR, G., MOUDLING, C., MURPHY, W., POTTER, H., STEWART, T. & TAUB, R. (1983). Translocations among antibody genes in human cancer, Science, 222, 765.CrossRefGoogle Scholar
  72. 71).
    ADAMS, J.M., GERONDAKIS, S., WEBB, E., CARCORAN, L.M. & CORY, S. (1983). Cellular myc oncogene is altered by chromosome translocation to an immunoglobulin locus in murine plasmacytoma and is rearranged similarly in human Burkitt lymphomas, Proc. Natl. Acad. Sci. USA, 80, 1982.CrossRefGoogle Scholar
  73. 72).
    KLEIN, G. & KLEIN, E. (1984). Oncogene activation and tumor progression, Carcinogenesis, 5, 429.CrossRefGoogle Scholar
  74. 73).
    SLAMON, D.J., DEKERNION, J.B., VERMA, I.M. & CLINE, M.J. (1984). Expression of cellular oncogenes in human malignancies, Science, 224, 256.CrossRefGoogle Scholar
  75. 74).
    PAYNE, G.S., BISHOP, J.M. & VARMUS, N.E. (1982). Multiple arrangements of viral DNA and an activated host oncogene in bursal lymphomas, Nature, 295, 209.CrossRefGoogle Scholar
  76. 75).
    TSICHLIS, P.N., STRAUSS, P.G. & HU, L.F. (1983). A common region for proviral DNA integration in MoMuLV-induced rat thymic lymphomas, Nature, 302, 445.CrossRefGoogle Scholar
  77. 76).
    YOSHIMURA, F.K. & LEVINE, K.L. (1983). AKR thymic lymphomas involving mink cell focus-inducing leukemia viruses have a common region of provirus integration, J. Virol., 45, 576.Google Scholar
  78. 77).
    KETTMANN, R., DESCHAMPS, J., CLEUTER, Y., COUEZ, D., BURNY, A. & MARBAIX, G. (1982). Leukemogenesis by bovine leukemia virus: Proviral DNA integration and lack of RNA expression of viral long terminal repeat and 3’ proximate cellular sequences, Proc. Natl. Acad. Sci. USA, 79, 2465.CrossRefGoogle Scholar
  79. 78).
    MILLER, J.M., MILLER, L.D., OLSON, C. & GILLETTE, K.S. (1969). Virus-like particles in phytohemagglutinin-stimulated lymphocyte cultures with reference to bovine lymphosarcoma, J. Natl. Cancer Inst., 43, 1297.Google Scholar
  80. 79).
    WESTAWAY, D., PAYNE, G. & VARMUS, H.E. (1984). Proviral deletions and oncogene base-substitutions in insertionally mutagenized c-myc alleles may contribute to the progression of avian bursal tumors, Proc. Natl. Acad. Sci. USA, 81, 843.CrossRefGoogle Scholar
  81. 80).
    KLEIN, G. (1983). Specific chromosomal translocations and the genesis of B-cell-derived tumors in mice and men, Cell, 32, 311CrossRefGoogle Scholar
  82. 81).
    ROWLEY, J.D. (1983). Human oncogene locations and chromosome aberrations, Nature, 301, 290.CrossRefGoogle Scholar
  83. 82).
    BATTEY, J., MOULDING, C., TAUB, R., MURPHY, W., STEWART, T., POTTER, H., LENOIR, G. & LEDER, P. (1983). The human c-myc oncogene: Structural consequences of translocation into the IgH locus in Burkitt lymphoma, Cell, 34, 779.CrossRefGoogle Scholar
  84. 83).
    GELMANN, E., PSALLIDOPOULOS, M.C., PAPAS, T.S. & Dalla-Favera, R. (1983). Identification of reciprocal translocation sites within the c-myc oncogene amd immunoglobulin p locus in a Burkitt lymphoma, Nature, 306, 799.CrossRefGoogle Scholar
  85. 84).
    CROCE, C.M., THIERFELDER, W., ERIKSON, J., NISHIKURA, K., FINAN, J., LENOIR, G.M. & NOWELL, P.C. (1983). Transcriptional activation of an unrearranged and untranslocated c-myc oncogene by translocation of a C) locus in Burkitt lymphoma cells, Proc. Natl. Acad. Sci. USA, 80, 6922.CrossRefGoogle Scholar
  86. 85).
    ERIKSON, J., Ar-Rushidi, A., DRWINGA, H.L., NOWELL, P.C. & CROCE, C.M. (1983). Transcriptional activation of the trans-located c-myc oncogene in Burkitt lymphoma, Proc. Natl. Acad. Sci. USA, 80, 820.CrossRefGoogle Scholar
  87. 86).
    HOLLIS, G.F., MITCHELL, K.F., BATTERY, J., POTTER, H., TAUB, R., LENOIR, G.M. & LEDER, P. (1984). A variant translocation places the a immunoglobulin genes 3’ to the c-myc oncogene in Burkitt’s lymphoma, Nature, 307, 752.CrossRefGoogle Scholar
  88. 87).
    DAVIS, M., MALCOLM, S. & RABBITTS, T.H. (1984). Chromosome translocation can occur on either side of the c-myc oncogene in Burkitt lymphoma cells, Nature, 308, 286.CrossRefGoogle Scholar
  89. 88).
    ERIKSON, J., NISHIKURA, K., Ar-Rushdi, A., FINAN, J., EMANUEL, B., LENOIR, G., NOWELL, P.C. & CROCE, C.M. (1983). Translocation of an immunoglobulin K locus to a region 3’ of an unrearranged c-myc oncogene enhances c-myc transcription, Proc. Natl. Acad. Sci. USA, 80, 7581.CrossRefGoogle Scholar
  90. 89).
    WESTIN, E.H., Wong-Staal, F., GELMANN, E.P., DALLA FAVERA, R., PAPAS, T.S., LAUTENBERGER, J.A., EVA, A., REDDY, E.P., TRONICK, S.R., AARONSON, S.A. & GALLO, R.C. (1982). Expression of cellular homologues of retroviral one genes in human hematopoietic cells, Proc. Natl. Acad. Sci. USA, 79, 2490.CrossRefGoogle Scholar
  91. 90).
    MAGUIRE, R.T., ROBINS, T.S., THORGERSSON, S.S. & HEILMAN, C.A. (1983). Expression of cellular myc and mos genes in undifferentiated B cell lymphomas of Burkitt and non-Burkitt types, Proc. Natl. Acad. Sci. USA, 80, 1947.CrossRefGoogle Scholar
  92. 91).
    HAMLYN, P.H. & RABBITTS, T.H. (1983). Translocation joins c- myc and immunoglobulin al genes in a Burkitt lymphoma revealing a third exon in the c-myc oncogene, Nature, 304, 135.CrossRefGoogle Scholar
  93. 92).
    TAUB, R., MOULDING, C., BATTEY, J., MURPHY, W., VASICEK, T., LENOIR, G.M. & LEDER, P. (1984). Activation and somatic mutation of the translocated c-myc gene in Burkitt lymphoma cells, Cell, 36, 339.CrossRefGoogle Scholar
  94. 93).
    KELLY, K., COCHRAN, B.H., STILES, C.D. & LEDER, P.(1983). Cell-specific regulation of the c-myc gene by lymphocyte mito-gens and platelet derived growth factor, Cell, 35, 603.CrossRefGoogle Scholar
  95. 94).
    RABBITTS, T.H., HAMLYN,P.H.& BAER, R. (1983). Altered nucleotide sequences of a translocated c-myc gene in Burkitt lymphoma, Nature, 306, 760.CrossRefGoogle Scholar
  96. 95).
    RABBITTS, T.H., FORSTER, A., HAMLYN, P. & BAER, R. (1983). Effect of somatic mutation within translocated c-myc genes in Burkitt’s lymphoma, Nature, 309, 593.Google Scholar
  97. 95a).
    GAZIN, C., DUPONT DE DINECHIN, S., HAMPE, A., MASSON, J.-M., MARTIN, P., STEHELIN, D. & GALIBERT, F. (1984). Nucleotide sequence of the human c-myc locus: provocative open reading frame within the first exon, EMBO J., 3, 383.Google Scholar
  98. 96).
    STANTON, L.W., FAHRLANDER, P.D., TESSER, P.M. & MARCU, K.B. (1984). Nucleotide sequence comparison of normal and trans-located murine c-myc genes, Nature, 310, 423.CrossRefGoogle Scholar
  99. 96).
    STANTON, L.W., FAHRLANDER, P.D., TESSER, P.M. & MARCU, K.B. (1984). Nucleotide sequence comparison of normal and trans-located murine c-myc genes, Nature, 310, 423.CrossRefGoogle Scholar
  100. 97).
    COPELAND, N.G. & COOPER, G.M. (1980). Transfection by DNAs of avian erythroblastosis virus and avian myelocytomatosis virus strain MC29, J. Virol., 33, 1199.Google Scholar
  101. 98).
    LAUTENBERGER, J.A., SCHULZ, R.A., GARON, C.F., TSICHLIS, P.H. & PAPAS, T.S. (1981). Molecular cloning of avian myeloblastosis virus (MC29) transforming sequences, Proc. Natl. Acad. Sci. USA, 78, 1518.CrossRefGoogle Scholar
  102. 99).
    QUADE, K. (1979). Transformation of mammalian cells by avian myelocytomatosis virus and avian erythroblastosis virus, Virology, 98, 461.CrossRefGoogle Scholar
  103. 100).
    GOUBIN, G., GOLDMAN, D.S., LUCE, J., NEIMAN, P.E. & COOPER, G.M. (1983). Molecular cloning and nucleotide sequence of a transforming gene detected by transfection of chicken B-cell lymphoma DNA, Nature, 302, 114.CrossRefGoogle Scholar
  104. 101).
    RUBIN, H. (1984). Chromosome aberratons and oncogenes: Cause or consequence in cancer, Nature, 309, 518.CrossRefGoogle Scholar
  105. 102).
    ERIKSON, J., FINAN, J., TSUJIMOTO, Y., NOWELL, P.C. & CROCE, C.(1984). The chromosome 14 breakpoint in neoplastic B cells with the t(11;14) translocation involves the immunoglobulin heavy chain locus, Proc. Natl. Acad. Sci. USA, 81, 4144.CrossRefGoogle Scholar
  106. 103).
    YUNIS, J.J., OKEN, M.D., KAPLAN, M.E., ENSURD, K.M., HOWE, R.R. & THEOLOGIDES, A. (1982). Distinctive chromosomal abnormalities in histologic subtypes of non-Hodgkin’s lymphoma, New Eng. J. of Med., 307, 1231.CrossRefGoogle Scholar
  107. 104).
    FIALKOW, R.J. & SINGER, J.W. (1984). Tracing development and cell lineages in human hemopoietic neoplasia. In: “Proceedings of the Dahlem Workshop on Leukemia”, Springer-Verlag, Berlin, Germany, in press.Google Scholar
  108. 105).
    DER, J.C., KRONTIRIS, T.G. & COOPER, G.M. (1982). Transforming genes of human bladder and lung carcinoma cell lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses, Proc. Natl. Acad. Sci. USA, 79, 3637.CrossRefGoogle Scholar
  109. 106).
    ELLIS, R.W., LOWY, D.R. & SCOLNICK, E.M. (1982). Mouse cells contain two distinct ras gene mRNA species that can be translated into a p21 one protein. In: “Advances in Viral Oncology, Volume 1”, G. Klein, ed., Raven Press, New York.Google Scholar
  110. 107).
    CAPON, D.J., CHEN, E.Y., LEVINSON, A.D., SEEBURG, P.H. & GOEDDEL, D.V. (1983). Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue, Nature, 302, 33.CrossRefGoogle Scholar
  111. 108).
    FINKEL, T., CHANNING, J.D. & COOPER, G.M. (1984). Activation of ras genes in human tumors does not affect localization, modification, or nucleotide binding properties of p21, Cell, 37, 151.CrossRefGoogle Scholar
  112. 109).
    REDDY, E.P., REYNOLDS, R.K., SANTOS, E. & BARBACID, M. (1982). A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene, Nature, 300, 149.CrossRefGoogle Scholar
  113. 110).
    FEINBERG, A.P., VOGELSTEIN, B., DROLLER, M.J., BAYLIN, S.B. & NELKIN, B.D. (1983). Mutation affecting the 12th amino acid of the c-Ha-ras oncogene product occurs infrequently in human cancer, Science, 220, 1175.CrossRefGoogle Scholar
  114. 111).
    SANTOS, E., Martin-Zanca, D., REDDY, E.P., PIEROTTI, M.A., DELLA PORTA, G. & BARBACID, M. (1984). Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient, Science, 223, 661.CrossRefGoogle Scholar
  115. 112).
    SAGER, R., TANAKA, K., LAU, C.C., EBINA, Y. & ANISOWICZ, A. (1983). Resistance of human cells to tumorigenesis induced by cloned transforming genes, Proc. Natl. Acad. Sci. USA, 80, 7601.CrossRefGoogle Scholar
  116. 113).
    HARVEY, J.J. & EAST, J. (1971). The murine sarcoma virus (MSV), Int. Rev. of Exp. Pathol., 10, 265.Google Scholar
  117. 114).
    LEVY, J.A. (1973). Demonstration of differences in murine sarcoma virus foci formed in mouse and rat cells under a soft agar overlay, J. Nat. Cancer Inst., 46, 1001.Google Scholar
  118. 115).
    AARONSON, S.A. & TODARO, G.I. (1970). Transformation and virus growth by murine sarcoma virus in human cells, Nature, 225, 458.CrossRefGoogle Scholar
  119. 116).
    AARONSON, S.A. & WEAVER, C.A. (1971). Characterization of murine sarcoma virus (Kirsten) transformation of mouse and human cells, J. Gen. Virol., 13, 245.CrossRefGoogle Scholar
  120. 117).
    KLEMENT, V., FRIEDMAN, M., MCALLISTER, R., Nelson-Rees, W. & HUEBNER, R.J. (1971). Differences in susceptibility of human cells to mouse sarcoma virus, J. Natl. Cancer Inst., 47, 65.Google Scholar
  121. 118).
    PFEFFER, L.M. & KOPEOLVICH, L. (1977). Differential genetic susceptibility of cultured human skin fibroblasts to transformation of Kirsten murine sarcoma virus, Cell, 10, 313.CrossRefGoogle Scholar
  122. 119).
    LEVY, J.A. (1975). Host range of murine xenotropic virus: Replication in avian cells, Nature, 253, 140.CrossRefGoogle Scholar
  123. 120).
    YUASA, Y., SRIVASTAVA, S.K., DUNN, C.Y., RHIM, J.S., REDDY, E.P. & AARONSON, S.A. (1983). Acquisition of transforming properties by alternative point mutations within c-bas/has human proto-oncogene, Nature, 303, 775.CrossRefGoogle Scholar
  124. 121).
    FUJITA, J., YOSHIDA, 0., YUASA, Y., RHIM, J.S., HATANAKA, M. & AARONSON, S.A. (1984). Ha-ras oncogenes are activated by somatic alterations in human urinary tract tumors, Nature, 309, 464.CrossRefGoogle Scholar
  125. 122).
    BALMAIN, A., RAMSDEN, M., BOWDEN, G.T. & SMITH, J. (1984). Activation of the mouse cellular Harvey-ras gene is chemically induced benign skin papillomas, Nature, 307, 658.CrossRefGoogle Scholar
  126. 123).
    SUKUMAR, S., NOTARIO, V., Martin-Zanca, D. & BARBACID, M. (1983). Induction of mammary carcinomas in rats by nitrosomethylurea involves malignant activation of H-ras-1 locus by single point mutations, Nature, 306, 658.CrossRefGoogle Scholar
  127. 124).
    HOLLIDAY, R. (1983). Cancer and cell senescence, Nature, 306, 742.CrossRefGoogle Scholar
  128. 125).
    FOGH, J., ed. (1975). “Human Tumor Cells In Vitro”,Plenum Press, New York.Google Scholar
  129. 125a).
    SALMON, S.E. (1980). Cloning of human tumor stem cells. Alan R. Liss, N.Y.Google Scholar
  130. 126).
    WIGLER, M., FASANO, O., TAPAROWSKY, E., POWERS, S., KATAOKA, T., BRINBAUM, D., SHIMIZU, K.F. & GOLDFARB, M. (1984). Structure and activation of ras genes. In: “Cancer Cells 2/Oncogenes and Viral Genes”, G.F. Vande Woude, A.J. Levine, W.C. Topp & J.D. Watson, eds., Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.Google Scholar
  131. 127).
    CAPON, D.J., SEEBURG, P.H., MCGRATH, J.P., HAYFLICK, J.S., EDMAN, U., LEVINSON, A.D. & GOEDDEL, D.V. (1983). Activation of Ki-ras 2 gene in human colon and lung carcinomas by two different point mutations, Nature, 304, 507.CrossRefGoogle Scholar
  132. 128).
    PULCIANI, S., SANTOS, E., LAUVER, A.V., LONG, L.K., AARONSON, S.A. & BARBACID, M. (1982). Oncogenes in solid human tumors, Nature, 300, 539.CrossRefGoogle Scholar
  133. 129).
    ALBINO, A.P., LE STRANGE, R., OLIFF, A.I., FURTH, M.E. & OLD, L.J. (1984). Transforming ras genes from human melanoma: A manifestation of tumor heterogeneity?, Nature, 308, 69.CrossRefGoogle Scholar
  134. 130).
    VOUSDEN, K.M. & MARSHALL, C.J. (1984). Three different activated ras genes in mouse tumours; evidence for oncogene activation during progression of a mouse lymphoma, EMBO J., 3, 913.Google Scholar
  135. 131).
    TAINSKY, M.A., COOPER, C.S., GIOVANELLA, B.C. & VANDE WOUDE, G.F. (1984). An activated ras N gene: Detected in late but not early passage human PAl teratocarcinoma cells, Science, 225, 643.CrossRefGoogle Scholar
  136. 132).
    MAISEL, J., KLEMENT, V., LAI, M.M.C., OSTERTAG, W. & DUESBERG, P.H. (1973). Ribonucleic acid components of murine sarcoma and leukemia viruses, Proc. Natl. Acad. Sci. USA, 70, 3536.CrossRefGoogle Scholar
  137. 133).
    ELLIS, R.W., DEFEO, D., FURTH, M.E. & SCOLNICK, E.M. (1982). Mouse cells contain two distinct ras gene mRNA species that can be translated into a p21 onc protein, Molec. Cell. Biol. 2, 1339.Google Scholar
  138. 134).
    PARADA, L.F., TABIN, C., SHIH, C. & WEINBERG, R.A. (1982). Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma ras gene, Nature, 297, 474.CrossRefGoogle Scholar
  139. 135).
    SCOLNICK, E.M., VASS, W.C., HOWK, R.S. & DUESBERG, P.H. (1979). Defective retrovirus-like 30S RNA species of rat and mouse cells are infectious if packaged by Type C helper virus, J. Virol., 29, 964.Google Scholar
  140. 136).
    TEMIN, H.M. (1983). We still don’t understand cancer, Nature, 302, 656.CrossRefGoogle Scholar
  141. 137).
    SPANDIDOS, D.A. & WILKIE, N.M. (1984). Malignant transformation of early passage rodent cells by a single mutated human oncogene, Nature, 310, 469.CrossRefGoogle Scholar
  142. 138).
    STEWART, T.A., PATTENGALE, P.K. & LEDER, P. (1984). Spontaneous mammary adenocarcinoma in transgenic mice that carry and express MTV/myc fusion genes, Cell, 38, 627.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Peter H. Duesberg
    • 1
  • Michael Nunn
    • 2
  • Nancy Kan
    • 3
  • Dennis Watson
    • 3
  • Peter H. Seeburg
    • 4
  • Takis Papas
    • 3
  1. 1.Department of Molecular BiologyUniversity of CaliforniaBerkeleyUSA
  2. 2.The Salk InstituteSan DiegoUSA
  3. 3.Laboratory of Molecular OncologyNational Cancer Institute, Frederick Cancer Research FacilityFrederickUSA
  4. 4.Genentech, Inc.South San FranciscoUSA

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