Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Apr;84(8):2117–2124. doi: 10.1073/pnas.84.8.2117

Cancer genes: rare recombinants instead of activated oncogenes (a review).

P H Duesberg
PMCID: PMC304600  PMID: 3550807

Abstract

The 20 known transforming (onc) genes of retroviruses are defined by sequences that are transduced from cellular genes termed protooncogenes or cellular oncogenes. Based on these sequences, viral onc 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 that viral onc genes and proto-onc genes are isogenic; that expression of proto-onc genes induces tumors; that activated proto-onc genes transform diploid cells upon transfection, like viral onc genes; and that diploid tumors exist. As yet, none of these predictions is confirmed. Instead: Structural comparisons between viral onc genes, essential retroviral genes, and proto-onc genes show that all viral onc genes are indeed new genes, rather than transduced cellular cancer genes. They are recombinants put together from truncated viral and truncated proto-onc genes. Proto-onc genes are frequently expressed in normal cells. To date, not one activated proto-onc gene has been isolated that transforms diploid cells. Above all, no diploid tumors with activated proto-onc genes have been found. Moreover, the probability of spontaneous transformation in vivo is at least 10(9) 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 viral onc genes. Here it is proposed that only rare truncations and illegitimate recombinations that alter the germ-line 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.

Full text

PDF
2117

Images in this article

2121Image
on p.2121

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aaronson S. A., Weaver C. A. Characterization of murine sarcoma virus (Kirsten) transformation of mouse and human cells. J Gen Virol. 1971 Nov;13(2):245–252. doi: 10.1099/0022-1317-13-2-245. [DOI] [PubMed] [Google Scholar]
  2. 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. 1985 Dec 12;318(6046):533–538. doi: 10.1038/318533a0. [DOI] [PubMed] [Google Scholar]
  3. Albino A. P., Le Strange R., Oliff A. I., Furth M. E., Old L. J. Transforming ras genes from human melanoma: a manifestation of tumour heterogeneity? Nature. 1984 Mar 1;308(5954):69–72. doi: 10.1038/308069a0. [DOI] [PubMed] [Google Scholar]
  4. Balmain A., Ramsden M., Bowden G. T., Smith J. Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas. Nature. 1984 Feb 16;307(5952):658–660. doi: 10.1038/307658a0. [DOI] [PubMed] [Google Scholar]
  5. Balmain A. Transforming ras oncogenes and multistage carcinogenesis. Br J Cancer. 1985 Jan;51(1):1–7. doi: 10.1038/bjc.1985.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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. 1986 Oct;6(10):3481–3489. doi: 10.1128/mcb.6.10.3481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Biggar R. J., Lee E. C., Nkrumah F. K., Whang-Peng J. Direct cytogenetic studies by needle aspiration of Burkitt's lymphoma in Ghana, West Africa. J Natl Cancer Inst. 1981 Oct;67(4):769–776. [PubMed] [Google Scholar]
  8. Bishop J. M. Cellular oncogenes and retroviruses. Annu Rev Biochem. 1983;52:301–354. doi: 10.1146/annurev.bi.52.070183.001505. [DOI] [PubMed] [Google Scholar]
  9. 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 Harb Symp Quant Biol. 1980;44(Pt 2):919–930. doi: 10.1101/sqb.1980.044.01.099. [DOI] [PubMed] [Google Scholar]
  10. Bishop J. M. Enemies within: the genesis of retrovirus oncogenes. Cell. 1981 Jan;23(1):5–6. doi: 10.1016/0092-8674(81)90263-4. [DOI] [PubMed] [Google Scholar]
  11. Bishop J. M. Oncogenes. Sci Am. 1982 Mar;246(3):80–92. doi: 10.1038/scientificamerican0382-80. [DOI] [PubMed] [Google Scholar]
  12. Boone C. W. Malignant hemangioendotheliomas produced by subcutaneous inoculation of Balb/3T3 cells attached to glass beads. Science. 1975 Apr 4;188(4183):68–70. doi: 10.1126/science.1114343. [DOI] [PubMed] [Google Scholar]
  13. Cichutek K., Duesberg P. H. Harvey ras genes transform without mutant codons, apparently activated by truncation of a 5' exon (exon -1). Proc Natl Acad Sci U S A. 1986 Apr;83(8):2340–2344. doi: 10.1073/pnas.83.8.2340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Diamond A., Cooper G. M., Ritz J., Lane M. A. Identification and molecular cloning of the human Blym transforming gene activated in Burkitt's lymphomas. Nature. 1983 Sep 8;305(5930):112–116. doi: 10.1038/305112a0. [DOI] [PubMed] [Google Scholar]
  15. Drake J. W. Comparative rates of spontaneous mutation. Nature. 1969 Mar 22;221(5186):1132–1132. doi: 10.1038/2211132a0. [DOI] [PubMed] [Google Scholar]
  16. Duesberg P. H. Activated proto-onc genes: sufficient or necessary for cancer? Science. 1985 May 10;228(4700):669–677. doi: 10.1126/science.3992240. [DOI] [PubMed] [Google Scholar]
  17. Duesberg P. H., Bister K., Moscovici C. Genetic structure of avian myeloblastosis virus, released from transformed myeloblasts as a defective virus particle. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5120–5124. doi: 10.1073/pnas.77.9.5120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Duesberg P. H., Bister K., Vogt P. K. The RNA of avian acute leukemia virus MC29. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4320–4324. doi: 10.1073/pnas.74.10.4320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Duesberg P. H. Retroviral transforming genes in normal cells? Nature. 1983 Jul 21;304(5923):219–226. doi: 10.1038/304219a0. [DOI] [PubMed] [Google Scholar]
  20. Duesberg P. H. Retroviruses as carcinogens and pathogens: expectations and reality. Cancer Res. 1987 Mar 1;47(5):1199–1220. [PubMed] [Google Scholar]
  21. Duesberg P. H. Transforming genes of retroviruses. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):13–29. doi: 10.1101/sqb.1980.044.01.005. [DOI] [PubMed] [Google Scholar]
  22. Duesberg P. H., Vogt P. K. Differences between the ribonucleic acids of transforming and nontransforming avian tumor viruses. Proc Natl Acad Sci U S A. 1970 Dec;67(4):1673–1680. doi: 10.1073/pnas.67.4.1673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Duesberg P., Vogt P. K., Beemon K., Lai M. Avian RNA tumor viruses: mechanism of recombination and complexity of the genome. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 2):847–857. doi: 10.1101/sqb.1974.039.01.099. [DOI] [PubMed] [Google Scholar]
  24. Feinberg A. P., Vogelstein B., Droller M. J., Baylin S. B., Nelkin B. D. Mutation affecting the 12th amino acid of the c-Ha-ras oncogene product occurs infrequently in human cancer. Science. 1983 Jun 10;220(4602):1175–1177. doi: 10.1126/science.6304875. [DOI] [PubMed] [Google Scholar]
  25. Frankel A. E., Fischinger P. J. Nucleotide sequences in mouse DNA and RNA specific for Moloney sarcoma virus. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3705–3709. doi: 10.1073/pnas.73.10.3705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Fujita J., Srivastava S. K., Kraus M. H., Rhim J. S., Tronick S. R., Aaronson S. A. Frequency of molecular alterations affecting ras protooncogenes in human urinary tract tumors. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3849–3853. doi: 10.1073/pnas.82.11.3849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Greig R. G., Koestler T. P., Trainer D. L., Corwin S. P., Miles L., Kline T., Sweet R., Yokoyama S., Poste G. Tumorigenic and metastatic properties of "normal" and ras-transfected NIH/3T3 cells. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3698–3701. doi: 10.1073/pnas.82.11.3698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Harnden D. G., Benn P. A., Oxford J. M., Taylor A. M., Webb T. P. Cytogenetically marked clones in human fibroblasts cultured from normal subjects. Somatic Cell Genet. 1976 Jan;2(1):55–62. doi: 10.1007/BF01539242. [DOI] [PubMed] [Google Scholar]
  29. 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. 1981 Jan 15;27(1):15–21. doi: 10.1002/ijc.2910270104. [DOI] [PubMed] [Google Scholar]
  30. Hayflick J., Seeburg P. H., Ohlsson R., Pfeifer-Ohlsson S., Watson D., Papas T., Duesberg P. H. Nucleotide sequence of two overlapping myc-related genes in avian carcinoma virus OK10 and their relation to the myc genes of other viruses and the cell. Proc Natl Acad Sci U S A. 1985 May;82(9):2718–2722. doi: 10.1073/pnas.82.9.2718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Heisterkamp N., Stam K., Groffen J., de Klein A., Grosveld G. Structural organization of the bcr gene and its role in the Ph' translocation. 1985 Jun 27-Jul 3Nature. 315(6022):758–761. doi: 10.1038/315758a0. [DOI] [PubMed] [Google Scholar]
  32. Huebner R. J., Todaro G. J. Oncogenes of RNA tumor viruses as determinants of cancer. Proc Natl Acad Sci U S A. 1969 Nov;64(3):1087–1094. doi: 10.1073/pnas.64.3.1087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ikawa S., Hagino-Yamagishi K., Kawai S., Yamamoto T., Toyoshima K. Activation of the cellular src gene by transducing retrovirus. Mol Cell Biol. 1986 Jul;6(7):2420–2428. doi: 10.1128/mcb.6.7.2420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Kan N. C., Flordellis C. S., Mark G. E., Duesberg P. H., Papas T. S. Nucleotide sequence of avian carcinoma virus MH2: two potential onc genes, one related to avian virus MC29 and the other related to murine sarcoma virus 3611. Proc Natl Acad Sci U S A. 1984 May;81(10):3000–3004. doi: 10.1073/pnas.81.10.3000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Karess R. E., Hayward W. S., Hanafusa H. Transforming protein encoded by the cellular information of recovered avian sarcoma viruses. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 2):765–771. doi: 10.1101/sqb.1980.044.01.082. [DOI] [PubMed] [Google Scholar]
  36. Klein G., Klein E. Oncogene activation and tumor progression. Carcinogenesis. 1984 Apr;5(4):429–435. doi: 10.1093/carcin/5.4.429. [DOI] [PubMed] [Google Scholar]
  37. Klein G., Ohno S., Rosenberg N., Wiener F., Spira J., Baltimore D. Cytogenetic studies on abelson-virus-induced mouse leukemias. Int J Cancer. 1980 Jun 15;25(6):805–811. doi: 10.1002/ijc.2910250617. [DOI] [PubMed] [Google Scholar]
  38. Klein G. The role of gene dosage and genetic transpositions in carcinogenesis. Nature. 1981 Nov 26;294(5839):313–318. doi: 10.1038/294313a0. [DOI] [PubMed] [Google Scholar]
  39. Knudson A. G., Jr Hereditary cancer, oncogenes, and antioncogenes. Cancer Res. 1985 Apr;45(4):1437–1443. [PubMed] [Google Scholar]
  40. Kraemer P. M., Ray F. A., Brothman A. R., Bartholdi M. F., Cram L. S. Spontaneous immortalization rate of cultured Chinese hamster cells. J Natl Cancer Inst. 1986 Apr;76(4):703–709. doi: 10.1093/jnci/76.4.703. [DOI] [PubMed] [Google Scholar]
  41. LEVAN A. Chromosomes in cancer tissue. Ann N Y Acad Sci. 1956 Mar 14;63(5):774–792. doi: 10.1111/j.1749-6632.1956.tb50892.x. [DOI] [PubMed] [Google Scholar]
  42. Land H., Parada L. F., Weinberg R. A. Cellular oncogenes and multistep carcinogenesis. Science. 1983 Nov 18;222(4625):771–778. doi: 10.1126/science.6356358. [DOI] [PubMed] [Google Scholar]
  43. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  44. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  45. Leder P., Battey J., Lenoir G., Moulding C., Murphy W., Potter H., Stewart T., Taub R. Translocations among antibody genes in human cancer. Science. 1983 Nov 18;222(4625):765–771. doi: 10.1126/science.6356357. [DOI] [PubMed] [Google Scholar]
  46. 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 Natl Acad Sci U S A. 1980 Apr;77(4):2018–2022. doi: 10.1073/pnas.77.4.2018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Littlefield J. W. NIH 3T3 cell line. Science. 1982 Oct 15;218(4569):214–216. doi: 10.1126/science.218.4569.214-b. [DOI] [PubMed] [Google Scholar]
  48. Lowy D. R., Willumsen B. M. The ras gene family. Cancer Surv. 1986;5(2):275–289. [PubMed] [Google Scholar]
  49. 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. Isr J Med Sci. 1985 Mar;21(3):296–301. [PubMed] [Google Scholar]
  50. Martin G. S., Duesberg P. H. 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. 1972 Feb;47(2):494–497. doi: 10.1016/0042-6822(72)90287-5. [DOI] [PubMed] [Google Scholar]
  51. 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 Natl Acad Sci U S A. 1978 Dec;75(12):5874–5878. doi: 10.1073/pnas.75.12.5874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. 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. 1986 Oct 30;140(2):699–705. doi: 10.1016/0006-291x(86)90788-6. [DOI] [PubMed] [Google Scholar]
  53. Naharro G., Robbins K. C., Reddy E. P. Gene product of v-fgr onc: hybrid protein containing a portion of actin and a tyrosine-specific protein kinase. Science. 1984 Jan 6;223(4631):63–66. doi: 10.1126/science.6318314. [DOI] [PubMed] [Google Scholar]
  54. Needleman S. W., Kraus M. H., Srivastava S. K., Levine P. H., Aaronson S. A. High frequency of N-ras activation in acute myelogenous leukemia. Blood. 1986 Mar;67(3):753–757. [PubMed] [Google Scholar]
  55. Newbold R. F., Overell R. W. Fibroblast immortality is a prerequisite for transformation by EJ c-Ha-ras oncogene. Nature. 1983 Aug 18;304(5927):648–651. doi: 10.1038/304648a0. [DOI] [PubMed] [Google Scholar]
  56. Nunn M. F., Seeburg P. H., Moscovici C., Duesberg P. H. Tripartite structure of the avian erythroblastosis virus E26 transforming gene. Nature. 1983 Nov 24;306(5941):391–395. doi: 10.1038/306391a0. [DOI] [PubMed] [Google Scholar]
  57. 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. 1985 Oct 30;146(2):307–314. doi: 10.1016/0042-6822(85)90014-5. [DOI] [PubMed] [Google Scholar]
  58. Pierce J. H., Aaronson S. A. BALB- and Harvey-murine sarcoma virus transformation of a novel lymphoid progenitor cell. J Exp Med. 1982 Sep 1;156(3):873–887. doi: 10.1084/jem.156.3.873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Rapp U. R., Cleveland J. L., Fredrickson T. N., Holmes K. L., Morse H. C., 3rd, Jansen H. W., Patschinsky T., Bister K. Rapid induction of hemopoietic neoplasms in newborn mice by a raf(mil)/myc recombinant murine retrovirus. J Virol. 1985 Jul;55(1):23–33. doi: 10.1128/jvi.55.1.23-33.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Ray F. A., Bartholdi M. F., Kraemer P. M., Cram L. S. Spontaneous in vitro neoplastic evolution: recurrent chromosome changes of newly immortalized Chinese hamster cells. Cancer Genet Cytogenet. 1986 Mar 1;21(1):35–51. doi: 10.1016/0165-4608(86)90199-8. [DOI] [PubMed] [Google Scholar]
  61. 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. 1982 Nov 11;300(5888):149–152. doi: 10.1038/300149a0. [DOI] [PubMed] [Google Scholar]
  62. 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 Natl Acad Sci U S A. 1986 Jan;83(1):33–37. doi: 10.1073/pnas.83.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Rous P. The challenge to man of the neoplastic cell. Science. 1967 Jul 7;157(3784):24–28. doi: 10.1126/science.157.3784.24. [DOI] [PubMed] [Google Scholar]
  64. 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 Natl Cancer Inst. 1983 Aug;71(2):365–375. [PubMed] [Google Scholar]
  65. Sager R., Tanaka K., Lau C. C., Ebina Y., Anisowicz A. Resistance of human cells to tumorigenesis induced by cloned transforming genes. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7601–7605. doi: 10.1073/pnas.80.24.7601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. 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 Natl Acad Sci U S A. 1986 Apr;83(7):2157–2161. doi: 10.1073/pnas.83.7.2157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Scolnick E. M., Parks W. P. Harvey sarcoma virus: a second murine type C sarcoma virus with rat genetic information. J Virol. 1974 Jun;13(6):1211–1219. doi: 10.1128/jvi.13.6.1211-1219.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Scolnick E. M., Rands E., Williams D., 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. 1973 Sep;12(3):458–463. doi: 10.1128/jvi.12.3.458-463.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Sharkey F. E., Fogh J. Considerations in the use of nude mice for cancer research. Cancer Metastasis Rev. 1984;3(4):341–360. doi: 10.1007/BF00051459. [DOI] [PubMed] [Google Scholar]
  70. Silverberg E. Cancer statistics. 1986. CA Cancer J Clin. 1986 Jan-Feb;36(1):9–25. doi: 10.3322/canjclin.36.1.9. [DOI] [PubMed] [Google Scholar]
  71. Stark G. R. DNA amplification in drug resistant cells and in tumours. Cancer Surv. 1986;5(1):1–23. [PubMed] [Google Scholar]
  72. 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. 1976 Mar 11;260(5547):170–173. doi: 10.1038/260170a0. [DOI] [PubMed] [Google Scholar]
  73. Stenman G., Delorme E. O., Lau C. C., Sager R. Transfection with plasmid pSV2gptEJ induces chromosome rearrangements in CHEF cells. Proc Natl Acad Sci U S A. 1987 Jan;84(1):184–188. doi: 10.1073/pnas.84.1.184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. 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. 1982 Nov 11;300(5888):143–149. doi: 10.1038/300143a0. [DOI] [PubMed] [Google Scholar]
  75. Tainsky M. A., Cooper C. S., Giovanella B. C., Vande Woude G. F. An activated rasN gene: detected in late but not early passage human PA1 teratocarcinoma cells. Science. 1984 Aug 10;225(4662):643–645. doi: 10.1126/science.6740333. [DOI] [PubMed] [Google Scholar]
  76. Terzi M., Hawkins T. S. Chromosomal variation and the establishment of somatic cell lines in vitro. Nature. 1975 Jan 31;253(5490):361–362. doi: 10.1038/253361a0. [DOI] [PubMed] [Google Scholar]
  77. Tsuchida N., Gilden R. V., Hatanaka M. Sarcoma-virus-related RNA sequences in normal rat cells. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4503–4507. doi: 10.1073/pnas.71.11.4503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Varmus H. E. The molecular genetics of cellular oncogenes. Annu Rev Genet. 1984;18:553–612. doi: 10.1146/annurev.ge.18.120184.003005. [DOI] [PubMed] [Google Scholar]
  79. Varmus H., Bishop J. M. Biochemical mechanisms of oncogene activity: proteins encoded by oncogenes. Introduction. Cancer Surv. 1986;5(2):153–158. [PubMed] [Google Scholar]
  80. Vousden K. H., Marshall C. J. Three different activated ras genes in mouse tumours; evidence for oncogene activation during progression of a mouse lymphoma. EMBO J. 1984 Apr;3(4):913–917. doi: 10.1002/j.1460-2075.1984.tb01905.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Wabl M., Burrows P. D., von Gabain A., Steinberg C. Hypermutation at the immunoglobulin heavy chain locus in a pre-B-cell line. Proc Natl Acad Sci U S A. 1985 Jan;82(2):479–482. doi: 10.1073/pnas.82.2.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Wang L. H., Duesberg P., 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. 1975 Oct;16(4):1051–1070. doi: 10.1128/jvi.16.4.1051-1070.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Wang L. H., Snyder P., Hanafusa T., Moscovici C., Hanafusa H. Comparative analysis of cellular and viral sequences related to sarcomagenic cell transformation. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 2):755–764. doi: 10.1101/sqb.1980.044.01.081. [DOI] [PubMed] [Google Scholar]
  84. Wang L. H. The gene order of avian RNA tumor viruses derived from biochemical analyses of deletion mutants and viral recombinants. Annu Rev Microbiol. 1978;32:561–592. doi: 10.1146/annurev.mi.32.100178.003021. [DOI] [PubMed] [Google Scholar]
  85. Watson D. K., Reddy E. P., Duesberg P. H., Papas T. S. 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, delta gag-myc. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2146–2150. doi: 10.1073/pnas.80.8.2146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Wolman S. R. Karyotypic progression in human tumors. Cancer Metastasis Rev. 1983;2(3):257–293. doi: 10.1007/BF00048481. [DOI] [PubMed] [Google Scholar]
  87. Zhou R. P., Kan N., Papas T., Duesberg P. Mutagenesis of avian carcinoma virus MH2: only one of two potential transforming genes (delta gag-myc) transforms fibroblasts. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6389–6393. doi: 10.1073/pnas.82.19.6389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. van der Hoorn F. A., Neupert B. The repressor sequence upstream of c-mos acts neither as polyadenylation site nor as transcription termination region. Nucleic Acids Res. 1986 Nov 25;14(22):8771–8783. doi: 10.1093/nar/14.22.8771. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES