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Medical Oncology and Tumor Pharmacotherapy

, Volume 4, Issue 3–4, pp 163–175 | Cite as

Cancer genes generated by rare chromosomal rearrangements rather than activation of oncogenes

  • Peter H. Duesberg
Viruses and Cancer Risks
  • 22 Downloads

Abstract

The 20 known transformingonc genes of retroviruses are defined by sequences that are transduced from cellular genes, termed proto-oncogenes or cellular oncogenes. Based on these sequences, viralonc genes have been postulated to be transduced cellular cancer genes and proto-onc genes have been postulated to be latent cancer genes that can be activated from within the cell to cause virus-negative tumors. The hypothesis is popular because it promises direct access to cellular cancer genes. However, the existence of latent cancer genes presents a paradox since such genes are clearly undesirable. The hypothesis predicts (i) that viralonc genes and proto-onc genes are isogenic, (ii) that expression of proto-onc genes induces tumors, (iii) that activated proto-onc genes transform diploid cells upon transfection, like viralonc genes, and (iv) that diploid tumors exist that differ from normal cells only in transcriptionally or mutationally activated proto-onc genes. As yet, none of these predictions is confirmed. Moreover, the probability of spontaneous transformationin vivo is at least 109 times lower than predicted from the mechanisms thought to activate proto-onc genes. Therefore the hypothesis, that proto-onc genes are latent cellular oncogenes, appears to be an overinterpretation of sequence homology to structural and functional homology with viralonc genes. Here it is proposed that only rare truncations and illegitimate recombinations that alter the germline configuration of cellular genes, generate viral and possibly cellular cancer genes. The clonal chromosome abnormalities that are consistently found in tumor cells are microscopic evidence for rearrangements that may generate cancer genes. The clonality indicates that the tumors are initiated with, and possibly by, these abnormalities as predicted by Boveri in 1914 (Zur Frage der Entstehung maligner Tumoren, Jena, Fischer).

Key words

Retroviralonc genes Proto-onc genes Illegitimate recombination Clonal chromosomal abnormalities 

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References

  1. 1.
    Duesberg P H: Cancer genes: rare recombinants instead of activated oncogenes.Proc natn Acad Sci USA 84 2117–2124 (1987).CrossRefGoogle Scholar
  2. 2.
    Wolman S R: Karyotypic progression in human tumors.Cancer Metast Rev 2, 257–293 (1983).CrossRefGoogle Scholar
  3. 3.
    Rowley J D: Introduction: consistent chromosomal alterations and oncogenes in human tumors.Cancer Surv 3, 355–357 (1984).Google Scholar
  4. 4.
    Trent J M: Chromosomal alterations in human solid tumors: implications of the stem cell model to cancer cytogenetics.Cancer Surv 3, 393–422 (1984).Google Scholar
  5. 5.
    Duesberg P H: Retroviruses as carcinogens and pathogens: expectations and reality.Cancer Res 47, 1199–1220 (1987).PubMedGoogle Scholar
  6. 6.
    Silverberg E, Lubera J: Cancer statistics.Ca-A.Cancer J. Clinics 36, 9–25 (1986).CrossRefGoogle Scholar
  7. 7.
    Duesberg P H: Retroviral transforming genes in normal cells?Nature 304, 219–226 (1983).PubMedCrossRefGoogle Scholar
  8. 8.
    Duesberg P H: Activated proto-onc, genes: sufficient or necessary for cancer?Science 228, 669–677 (1985).PubMedCrossRefGoogle Scholar
  9. 9.
    Weiss R, Teich N, Varmus H, Coffin J (1985) (eds):RNA Tumor Viruses: Molecular Biology of Tumor Viruses, 2nd edn., Cold Spring Harbor, NY, Cold Spring Harbor Press (1985).Google Scholar
  10. 10.
    Duesberg P H, Vogt P K: Differences between the ribonucleic acids of transforming and nontransforming avian tumor viruses.Proc natn Acad Sci USA 67, 1673–80 (1970).CrossRefGoogle Scholar
  11. 11.
    Martin G S, Duesberg P H: The a-subunit on the RNA of transforming avian tumor viruses. I. Occurrence in different virus strains. II. Spontaneous loss resulting in nontransforming variants.Virology 47, 494–497 (1972).PubMedCrossRefGoogle Scholar
  12. 12.
    Weiss R, Teich N, Varmus H, Coffin J (eds):RNA Tumor Viruses: Molecular Biology of Tumor Viruses Cold Spring Harbor, NY, Cold Spring Harbor Press (1982).Google Scholar
  13. 13.
    Duesberg P H: Transforming genes of retroviruses.44th Cold Spring Harbor Symp Quant Biol, p. 13–27 (1979).Google Scholar
  14. 14.
    Scolnick E M, Rands F, Williams P, Parks W P: Studies on the nucleic acid sequences of Kirsten sarcoma virus. A model for formation of a mammalian RNA-containing sarcoma virus.J Virol 12, 458–463 (1973).PubMedGoogle Scholar
  15. 15.
    Scolnick E M, Parks W P: Harvey sarcoma virus. A second murine type C sarcoma virus with rat genetic information.J Virol 13, 1211–1219 (1974).PubMedGoogle Scholar
  16. 16.
    Tsuchida N, Gilden R V, Hatanaka M: Sarcoma-virus-related RNA sequences in normal rat cells.Proc natn Acad Sci USA 71 4503–4507 (1974).CrossRefGoogle Scholar
  17. 17.
    Frankel A E, Fischinger P J: Nucleotide sequences in mouse DNA and RNA specific for Moloney sarcoma virus.Proc natn Acad Sci USA 73, 3705–3709 (1976).CrossRefGoogle Scholar
  18. 18.
    Stehelin D, Varmus H E, Bishop J M, Vogt P K: DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA.Nature 260, 170–173 (1976).PubMedCrossRefGoogle Scholar
  19. 19.
    Watson D K, Reddy E P, Duesberg P H, Papas T S: Nucleotide sequence analysis of the chickenc-myc gene reveals homologous and unique regions by comparison with the transforming gene of avian myelocytomatosis virus MC29,gag-myc.Proc natn Acad Sci USA 80, 2146–2150 (1983).CrossRefGoogle Scholar
  20. 20.
    Bishop J M, Courtneidge S A, Levinson A D, Oppermann H, Quintrell N, Sheiness D K, Weiss S R, Varmus H E: Origin and function of avian retrovirus transforming genes.Cold Spring Harbor Symp Quant Biol 44, 919–930 (1979).Google Scholar
  21. 21.
    Karess R E, Hayward W S, Hanafusa H: Transforming protein encoded by the cellular information of recovered avian sarcoma viruses.Cold Spring Harbor Symp Quant Biol 44, 765–771 (1979).Google Scholar
  22. 22.
    Wang L-H, Synder P, Hanafusa T, Moscovici C, Hanafusa H: Comparative analysis of cellular and viral sequences related to sarcomagenic cell transformation.Cold Spring Harbor Symp Quant Biol 44, 755–764 (1979).Google Scholar
  23. 23.
    Bishop J M: Enemies within: the genesis of retrovirus oncogenes.Cell 23, 5–6 (1981).PubMedCrossRefGoogle Scholar
  24. 24.
    Klein G: The role of gene dosage and genetic transposition in carcinogenesis.Nature 294, 313–318 (1981).PubMedCrossRefGoogle Scholar
  25. 25.
    Bishop J M, Varmus H: Functions and origins of retroviral transforming genes in RNA tumor viruses, in Weiss Ret al. (eds.):RNA Tumor Viruses; Molecular Biology of Tumor Viruses, pp. 999–1108. Cold Spring Harbor, NY, Cold Spring Harbor Press (1982).Google Scholar
  26. 26.
    Bishop J M: ‘Oncogenes’.Sci Am 246, 80–90 (1982).PubMedCrossRefGoogle Scholar
  27. 27.
    Bishop J M: Cellular oncogenes and retroviruses.Ann Rev Biochem 52, 301–354 (1983).PubMedCrossRefGoogle Scholar
  28. 28.
    Varmus H, Bishop J M: Introduction. Biochemical mechanisms of oncogene activity: proteins encoded by oncogenes.Cancer Surv 5, 153–158 (1986).PubMedGoogle Scholar
  29. 29.
    Weiss R A: The oncogene concept.Cancer Rev 2, 1–17 (1986).Google Scholar
  30. 30.
    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: Mechanism of activation of a human oncogene.Nature 300, 143–149 (1982).PubMedCrossRefGoogle Scholar
  31. 31.
    Reddy E P, Reynolds R K, Santos E, Barbacid M: A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene.Nature 300, 149–152 (1982).PubMedCrossRefGoogle Scholar
  32. 32.
    Leder P, Battey J, Lenoir G, Moulding C, Murphy W, Potter M, Stewart T, Taub R: Translocations among antibody genes in human cancer.Science 227, 765–771 (1983).CrossRefGoogle Scholar
  33. 33.
    Knudson A G, Jr: Hereditary cancer, oncogenes and antioncogenes.Cancer Res 45, 1437–1443 (1985).PubMedGoogle Scholar
  34. 34.
    Huebner R J, Todaro G: Oncogenes of RNA tumor viruses as determinants of cancer.Proc natn Acad Sci USA 64, 1087–1094 (1969).CrossRefGoogle Scholar
  35. 35.
    Pitot H C:Fundamentals of Oncology. New York, Dekker, (1978).Google Scholar
  36. 36.
    Klein G, Ohno S, Rosenberg N, Wiener F, Spira J, Baltimore D: Cytogenic studies on Abelson-virus-induced mouse leukemias.Int J Cancer 25 805–811 (1980).PubMedCrossRefGoogle Scholar
  37. 37.
    Levan A: Chromosomes in cancer tissue.Ann NY Acad Sci 63, 774–792 (1956).PubMedCrossRefGoogle Scholar
  38. 38.
    Feinberg A P, Vogelstein M J, Droller S, Baylin B, Nelkin B D: Mutation affecting the 12th amino acid of the c-Ha-ras oncogene product occurs infrequently in human cancer.Science 220, 1175–1177.Google Scholar
  39. 39.
    Fujita J, Srivastava S, Kraus M, Rhim J S, Tronick S R, Aaronson S A: Frequency of molecular alterations affectingras proto-oncogenes in human urinary tract tumors.Proc natn Acad Sci USA 82, 3849–3853 (1985).CrossRefGoogle Scholar
  40. 40.
    Milici A, Blick M, Murphy E, Gutterman J U: “c-K-ras codon 12 GGT-CGT point mutation an infrequent event in human lung cancer.Biochem biophys Res Commun 140, 699–705.Google Scholar
  41. 41.
    Cichutek K, Duesberg P H: Harveyras genes transform without mutant codons, apparently activated by truncation of a 5′ exon (exon-1).Proc natn Acad Sci USA 83, 2340–2344 (1986).CrossRefGoogle Scholar
  42. 42.
    Lowy D R, Willumsen B W: Theras gene family.Cancer Surv 5, 275–289 (1986).PubMedGoogle Scholar
  43. 43.
    Marshall C: Human Oncogenes, in Weiss Ret al. (eds):RNA Tumor Viruses; Molecular Biology of Tumor Viruses, pp. 487–558. Cold Spring Harbor, NY, Cold Spring Harbor Press (1985).Google Scholar
  44. 44.
    Barbacid M: Mutagens, oncogenes and cancer.Trends Gen 2, 188–192 (1986).CrossRefGoogle Scholar
  45. 45.
    Needleman S W, Kraus M H, Srivastava S K, Levine P H, Aarsonson S A: High frequency of N-ras activation in acute myelogenous leukemia.Blood 67, 753–757 (1986).PubMedGoogle Scholar
  46. 46.
    Hastings R J, Franks L M: Chromosome pattern, growth in agar and tumorigenicity in nude mice of four human bladder carcinoma cell lines.Int J Cancer 27, 15–21 (1981).PubMedCrossRefGoogle Scholar
  47. 47.
    Wabl M, Burrows P D, von Gabain A, Steinberg A: Hypermutation at the immunoglobulin heavy chain locus in a pre-B cell line.Proc natn Acad Sci USA 82, 479–482 (1984).CrossRefGoogle Scholar
  48. 48.
    Drake J W: Comparative rates of spontaneous mutation.Nature 221 1132 (1969).PubMedCrossRefGoogle Scholar
  49. 49.
    Sharkey F E, Fogh J: Considerations in the use of nude mice for cancer research.Cancer Metast Rev 3, 341–360 (1984).CrossRefGoogle Scholar
  50. 50.
    Kinlen L J: Immunosuppressive therapy and cancer.Cancer Surv 1, 565–583 (1982).Google Scholar
  51. 51.
    Sagar R, Tanaka K, Lau C C, Ebina Y, Anisowicz A: Resistance of human cells to tumorigenesis induced by cloned transforming genes.Proc natn Acad Sci 80, 7601–7605 (1983).CrossRefGoogle Scholar
  52. 52.
    Land H, Parada L F, Weinberg R A: Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes.Nature 304, 596–602 (1983).PubMedCrossRefGoogle Scholar
  53. 53.
    Land H, Parada L F, Weinberg R A: Cellular oncogenes and multistep carcinogenesis.Science 222, 771–778 (1983).PubMedCrossRefGoogle Scholar
  54. 54.
    Newbold R F, Overell R W: Fibroblast immortality is a prerequisite for transformation by EJ c-Ha-ras oncogene.Nature 304, 648–651 (1983).PubMedCrossRefGoogle Scholar
  55. 55.
    Boone C W: Malignant hemangioendotheliomas produced by subcutaneous inoculation of BALB/3T3 cells attached to glass beads.Science 188, 68–70 (1975)PubMedCrossRefGoogle Scholar
  56. 56.
    Littlefield J W: NIH/3T3 cell line.Science 218, 214–216 (1982).PubMedCrossRefGoogle Scholar
  57. 57.
    Greig R G, Koestler T P, Trayner D L, Corwin S P, Miles L, Kline T, Sweet R, Yokoyama S, Poste G: Tumorigenic and metastatic properties of ‘normal’ andras-transfected NIH/3T3 cells.Proc natn Acad Sci USA 82, 3698–3701 (1985).CrossRefGoogle Scholar
  58. 58.
    Rubin H, Chu B M, Arnstein P: Heritable variations in growth potential and morphology within a clone of Balb/3T3 cells and their relation to tumor formation.J natn Cancer Inst 71, 365–373 (1983).Google Scholar
  59. 59.
    Spandidos D A, Wilkie N M:In vitro malignant transformation of early passage rodent cells by a single mutated human oncogene.Nature 310, 469–475 (1984).PubMedCrossRefGoogle Scholar
  60. 60.
    Stenman G, Delorme E O, Lau C C, Sager R: Transfection with plasmid pSV2gptEJ induces chromosome rearrangements in CHEF cells.Proc natn Acad Sci USA 84, 184–188 (1987).CrossRefGoogle Scholar
  61. 61.
    Reynolds S H, Stowers S J, Maronpot R R, Anderson M W, Aaronson S A: Detection and identification of activated oncogenes in spontaneously occurring benign and malignant hepatocellular tumors of the B6C3F1 mouse.Proc natn Acad Sci USA 83, 33–37 (1986).CrossRefGoogle Scholar
  62. 62.
    Balmain A, Ramsden M, Bowden G T, Smith J: Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas.Nature 307, 658–660 (1984).PubMedCrossRefGoogle Scholar
  63. 63.
    Balmain A, Pragnell I B: Mouse skin carcinomas inducedin vivo by chemical carcinogens have a transforming Harvey-ras oncogene.Nature 304, 596–602 (1983).CrossRefGoogle Scholar
  64. 64.
    Klein G, Klein E: Oncogene activation and tumor progression.Carcinogenesis 5 429–435 (1984).PubMedCrossRefGoogle Scholar
  65. 65.
    Balmain A: Transformingras oncogenes and multistage carcinogenesis.Br J Cancer 51, 1–7 (1985).PubMedGoogle Scholar
  66. 66.
    Burns F J, Vanderlaan M, Snyder E, Albert R E: Induction and progression kinetics of mouse skin papillomas, in Slaga T J, Sivac A, Boutwell R K (eds):Carcinogenesis, Vol. 2,Mechanisms of Tumor Promotion and Cocarcinogenesis, pp. 91–96, New York, Raven Press (1978).Google Scholar
  67. 67.
    Albino A P, Le Strange A I, Oliff M I, Furth M E, Old L J: Transformingras genes from human melanoma: a manifestation of tumor heterogeneity?Nature 308, 69–72 (1984).PubMedCrossRefGoogle Scholar
  68. 68.
    Tainsky M A, Cooper G S, Giovanella B C, Vande Woude G F: An activatedras N gene: detected in late but not early passage human teratocarcinoma cells.Science 225, 643–645 (1984).PubMedCrossRefGoogle Scholar
  69. 69.
    Vousden K H, Marshall C J: Three different activatedras genes in mouse tumors: evidence for oncogene activation during progression of a mouse lymphoma.EMBO J 3, 913–917 (1984).PubMedGoogle Scholar
  70. 70.
    Aaronson S A, Weaver C A: Characterization of murine sarcoma virus (Kirsten) transformation of mouse and human cells.J gen Virol 13, 245–252 (1971).PubMedCrossRefGoogle Scholar
  71. 71.
    Hoelzer-Pierce J, Aaronson S A: BALB- and Harvey-murine sarcoma virus transformation of a novel lymphoid progenitor cell.J exp Med 156, 873–887 (1982).CrossRefGoogle Scholar
  72. 72.
    Rapp U R, Cleveland J L, Fredrickson T N, Holmes K L, Morse H C III, Jansen H W, Patschinsky T, Bister K: Rapid induction of hemopoietic neoplasms in newborn mice by araf(mil)/myc recombinant murine retrovirus.J Virol 55, 23–33 (1985).PubMedGoogle Scholar
  73. 73.
    Adams J M, Harris A W, Pinkert C A, Corcoran L M, Alexander W S, Cory S, Palmiter R D, Brinster R L: The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice.Nature 318, 533–538 (1985).PubMedCrossRefGoogle Scholar
  74. 74.
    Biggar R J, Lee E C, Nkrumah F K, Whang-Peng J: Direct cytogenetic studies by needle stick aspiration of Burkitt's lymphoma in Ghana, West Africa.J natn Cancer Inst 67, 769–776 (1981).Google Scholar
  75. 75.
    Sprent J: Migration and life span of lymphocytes, in Loor F, Roelants G E (eds):B and T Cells In Immune Recognition, pp. 59–82. New York, John Wiley (1977).Google Scholar
  76. 76.
    Stark G R: DNA amplification in drug resistant cells and in tumours.Cancer Surv 5, 1–23 (1986).PubMedGoogle Scholar
  77. 77.
    Schimke R T, Sherwood S W, Hill A B, Johnston R N: Overreplication and recombination of DNA in higher eukaryotes: potential consequences and biological implications.Proc natn Acad Sci USA 83, 2157–2161 (1986).CrossRefGoogle Scholar
  78. 78.
    Heisterkamp N, Stam K, Groffen J, De Klein A, Grosveld G: Structural organization of thebcr gene and its role in the Ph' translocation.Nature 315, 758–761 (1985).PubMedCrossRefGoogle Scholar
  79. 79.
    Kraemer P M, Ray F A, Brothman A R, Bartholdi M F, Cram L S: Spontaneous immortalization rate of cultured Chinese hamster cells.J. natn Cancer Inst 76, 703–709 (1986).Google Scholar
  80. 80.
    Ray F A, Bartholdi, M F, Kraemer P M, Cram L S: Spontaneousin vitro neoplastic evolution: recurrent chromosome changes of newly immortalized Chinese hamster cells.Cancer genet Cytogenet 21, 35–51 (1986).PubMedCrossRefGoogle Scholar
  81. 81.
    Terzi M, Hawkins T S C: Chromosomal variation and the establishment of somatic cell linesin vitro.Nature 253, 361–362 (1975).PubMedCrossRefGoogle Scholar
  82. 82.
    Harnden D G, Benn P A, Oxford J M, Taylor A M R, Webb T P: Cytogenetically marked clones in human fibroblasts cultured from normal subjects.Som cell Genet 2, 55–62 (1976).CrossRefGoogle Scholar
  83. 83.
    Martin G M, Smith A C, Ketterer D J, Ogburn C E, Disteche C M: Increased chromosomal aberrations in first metaphases of cells isolated from the kidneys of aged mice.Israel J med Sci 21, 296–301 (1985).PubMedGoogle Scholar
  84. 84.
    Hook E B: The impact of aneuploidy upon public health mortality and morbidity associated with human chromosome abnormalities, in Dellarco V L, Voytek P E, Hollaender A (eds):Aneuploidy: Etiology and Mechanisms, pp. 7–33. New York and London: Plenum Press (1985).Google Scholar
  85. 85.
    Dzarlieva R T, Fusenig N E: Tumor promoter 12-o-tetradecanoyl-phorbol-13-acetate enhances sister chromatid exchanges and numerical and structural chromosome aberrations in primary mouse epidermal cell cultures.Cancer Lett 16, 7–17 (1982).PubMedCrossRefGoogle Scholar
  86. 86.
    Petersson H, Mitelman F: Nonrandomde novo chromosome aberrations in human lymphocytes and amniotic cells.Hereditas 102, 33–38 (1985).PubMedCrossRefGoogle Scholar
  87. 87.
    Diamond A, Cooper G M, Ritz J, Lane M-A: Identification and molecular cloning of the human B-lym transforming gene activated in Burkitt's lymphomas.Nature 305, 112–116 (1983)PubMedCrossRefGoogle Scholar
  88. 88.
    Varmus H: The molecular genetics of cellular oncogenes.Ann Rev Genet 18, 553–612 (1984).PubMedCrossRefGoogle Scholar
  89. 89.
    Duesberg P H, Bister K, Vogt P K: The RNA of avian acute leukemia virus MC29.Proc natn Acad Sci 74, 4320–4324 (1977).CrossRefGoogle Scholar
  90. 90.
    Mellon P, Pawson A, Bister K, Martin G S, Duesberg P H: Specific RNA sequences and gene products of MC29 avian acute leukemia virus.Proc natn Acad Sci USA 75, 5874–5878 (1978).CrossRefGoogle Scholar
  91. 91.
    Wang L-H, Duesberg P H, Beemon K, Vogt P K: Mapping RNase T1-resistant oligonucleotides of avian tumor virus RNAs: sarcoma-specific oligonucleotides are near the poly(A) end and oligonucleotides common to sarcoma and transformation-defective viruses are at the poly(A) end.J. Virol 16, 1051–1070 (1975).PubMedGoogle Scholar
  92. 92.
    Wang L-H: The gene order of avian RNA tumor viruses derived from biochemical analyses of deletion mutants and viral recombinants.Ann Rev Microbiol 32, 561–592 (1978).CrossRefGoogle Scholar
  93. 93.
    Kan N C, Flordellis C S, Mark G E, Duesberg P H, Papas T S: Nucleotide sequence of avian carcinoma virus MH2: two potentialonc genes, one related to avian virus MC29 and the other related to murine sarcoma virus 3611.Proc natn Acad Sci USA 81, 3000–3004 (1984).CrossRefGoogle Scholar
  94. 94.
    Zhou R-P, Kan N, Papas T, Duesberg P: Mutagenesis of avian carcinoma virus MH2: only one of two potential transforming genes (gag-myc) transforms fibroblasts.Proc natn Acad Sci USA 82, 6389–6393 (1985).CrossRefGoogle Scholar
  95. 95.
    Hayflick J, Seeburg P H, Ohlsson R, Pfeifer-Ohlsson S, Watson D, Papas T, Duesberg P H: Nucleotide sequence of two overlappingmyc-related genes in avian carcinoma virus OK10 and their relation to themyc genes of other viruses and the cell.Proc natn Acad Sci USA 82, 2718–2722 (1985).CrossRefGoogle Scholar
  96. 96.
    Duesberg P H, Bister K, Moscovici C: Genetic structure of avian myeloblastosis virus, released from transformed myeloblasts as a defective virus particle.Proc natn Acad Sci USA 77, 5120–5124 (1980).CrossRefGoogle Scholar
  97. 97.
    Lee W-H, Bister K, Pawson A, Robins T, Moscovici C, Duesberg P H: Fujinami sarcoma virus: an avian RNA tumor virus with a unique transforming gene.Proc natn Acad Sci USA 77, 2018–2022 (1980).CrossRefGoogle Scholar
  98. 98.
    Bentley D L, Groudine M: Novel promoter upstream of the human c-myc gene and regulation of c-myc expression in B-cell lymphomas.Mol cell Biol 6, 3481–3489 (1986).PubMedGoogle Scholar
  99. 99.
    Duesberg P, Vogt P K, Beemon K, Lai M: Avian RNA tumor viruses: mechanism of recombination and complexity of the genome.Cold Spring Harbor Symp Quant Biol 39, 847–857 (1974).Google Scholar
  100. 100.
    Nunn M F, Seeburg P H, Moscovici C, Duesberg P H: Tripartite structure of the avian erythroblastosis virus E26 transforming gene.Nature 306, 391–395 (1983).PubMedCrossRefGoogle Scholar
  101. 101.
    Pfaff S L, Zhou R-P, Young J C, Hayflick J, Duesberg P H: Defining the borders of the chicken proto-fps gene, a precursor of Fujinami sarcoma virus.Virology 146, 307–314 (1985).PubMedCrossRefGoogle Scholar
  102. 102.
    van der Hoorn A, Neupert B: The repressor sequence upstream of c-mos acts neither as polyadenylation site nor as transcription termination region.Nucleic acids Res 14, 8771–8782 (1986).PubMedCrossRefGoogle Scholar
  103. 103.
    Ikawa S, Hagino-Yamagishi K, Kawai S, Yamamoto T, Toyoshima K: Activation of the cellularsrc gene by transducing retrovirus.Mol cell Biol 6, 2420–2428 (1986).PubMedGoogle Scholar
  104. 104.
    Naharro G, Robbins K C, Reddy E P: Gene product of v-frg onc: hybrid protein containing a portion of actin and a tyrosin-specific protein kinase.Science 223, 63–66 (1984).PubMedCrossRefGoogle Scholar
  105. 105.
    Boveri T:Zur Frage der Entstehung maligner Tumoren. Jena, Fischer (1914).Google Scholar
  106. 106.
    Klein G: Specific chromosomal translocations and the genesis of B-cell-derived tumors in mice and men.Cell 32, 311–315 (1983).PubMedCrossRefGoogle Scholar
  107. 107.
    Dracopoli N C, Houghton A N, Old L J: Loss of polymorphic restriction fragments in malignant melanoma: implications for tumor heterogeneity.Proc natn Acad Sci USA 82, 1470–1474 (1985).CrossRefGoogle Scholar
  108. 108.
    Rous P: The challenge to man of the neoplastic cell.Science 157, 24–28 (1967).PubMedCrossRefGoogle Scholar
  109. 109.
    Cairns J: Cancer, science and society. San Francisco, Freeman (1978).Google Scholar
  110. 110.
    Zinder N D: Infective heredity in bacteria.Cold Spring Harbor Symp Quant Biol 18, 261–269 (1953).PubMedGoogle Scholar

Copyright information

© Pergamon Press Ltd. 1987

Authors and Affiliations

  • Peter H. Duesberg
    • 1
  1. 1.Department of Molecular BiologyUniversity of California, BerkeleyBerkeleyU.S.A.

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