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. 1987 Aug;84(16):5660–5664. doi: 10.1073/pnas.84.16.5660

Isolation of a rearranged human transforming gene following transfection of Kaposi sarcoma DNA.

P Delli Bovi, C Basilico
PMCID: PMC298922  PMID: 3475697

Abstract

By transfecting high molecular weight DNA from a Kaposi sarcoma lesion into murine NIH 3T3 cells, we have identified and molecularly cloned a set of human DNA sequences capable of inducing focus formation, growth in agar, and tumorigenicity in these cells. The human DNA sequences present in primary, secondary, and tertiary NIH 3T3 transformants encompass about 32 kilobases (kb) and contain four rearrangements with respect to normal human DNA and a portion of the c-fms protooncogene (FMS in human gene nomenclature). However, the minimal transforming region (6.6 kb) identified in our cloned DNA borders on the c-fms DNA region but does not contain c-fms coding sequences. The fms sequences are also not represented in the two transcripts (approximately equal to 1.2 and 3.5 kb) detected in NIH 3T3 transformants; however, they might provide elements regulating expression. Hybridization to several known oncogene probes and preliminary sequencing data indicate that we have identified a previously unrecognized "activated" oncogene. Since the rearrangements present in our cloned DNA sequences are not detectable in the original Kaposi tumor DNA used for transfection, it is possible that this oncogene was generated during gene transfer.

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Selected References

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

  1. Basilico C., Gattoni S., Zouzias D., Valle G. D. Loss of integrated viral DNA sequences in polyomatransformed cells is associated with an active viral A function. Cell. 1979 Jul;17(3):645–659. doi: 10.1016/0092-8674(79)90272-1. [DOI] [PubMed] [Google Scholar]
  2. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  3. Colbère-Garapin F., Horodniceanu F., Kourilsky P., Garapin A. C. A new dominant hybrid selective marker for higher eukaryotic cells. J Mol Biol. 1981 Jul 25;150(1):1–14. doi: 10.1016/0022-2836(81)90321-1. [DOI] [PubMed] [Google Scholar]
  4. Coussens L., Van Beveren C., Smith D., Chen E., Mitchell R. L., Isacke C. M., Verma I. M., Ullrich A. Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. Nature. 1986 Mar 20;320(6059):277–280. doi: 10.1038/320277a0. [DOI] [PubMed] [Google Scholar]
  5. Delli Bovi P., Donti E., Knowles D. M., 2nd, Friedman-Kien A., Luciw P. A., Dina D., Dalla-Favera R., Basilico C. Presence of chromosomal abnormalities and lack of AIDS retrovirus DNA sequences in AIDS-associated Kaposi's sarcoma. Cancer Res. 1986 Dec;46(12 Pt 1):6333–6338. [PubMed] [Google Scholar]
  6. Donner L., Fedele L. A., Garon C. F., Anderson S. J., Sherr C. J. McDonough feline sarcoma virus: characterization of the molecularly cloned provirus and its feline oncogene (v-fms). J Virol. 1982 Feb;41(2):489–500. doi: 10.1128/jvi.41.2.489-500.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fasano O., Birnbaum D., Edlund L., Fogh J., Wigler M. New human transforming genes detected by a tumorigenicity assay. Mol Cell Biol. 1984 Sep;4(9):1695–1705. doi: 10.1128/mcb.4.9.1695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Friedman-Kien A. E. Disseminated Kaposi's sarcoma syndrome in young homosexual men. J Am Acad Dermatol. 1981 Oct;5(4):468–471. doi: 10.1016/s0190-9622(81)80010-2. [DOI] [PubMed] [Google Scholar]
  9. Frischauf A. M., Lehrach H., Poustka A., Murray N. Lambda replacement vectors carrying polylinker sequences. J Mol Biol. 1983 Nov 15;170(4):827–842. doi: 10.1016/s0022-2836(83)80190-9. [DOI] [PubMed] [Google Scholar]
  10. Goldfarb M., Shimizu K., Perucho M., Wigler M. Isolation and preliminary characterization of a human transforming gene from T24 bladder carcinoma cells. Nature. 1982 Apr 1;296(5856):404–409. doi: 10.1038/296404a0. [DOI] [PubMed] [Google Scholar]
  11. Gottlieb G. J., Ackerman A. B. Kaposi's sarcoma: an extensively disseminated form in young homosexual men. Hum Pathol. 1982 Oct;13(10):882–892. doi: 10.1016/s0046-8177(82)80047-6. [DOI] [PubMed] [Google Scholar]
  12. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  13. Hampe A., Gobet M., Sherr C. J., Galibert F. Nucleotide sequence of the feline retroviral oncogene v-fms shows unexpected homology with oncogenes encoding tyrosine-specific protein kinases. Proc Natl Acad Sci U S A. 1984 Jan;81(1):85–89. doi: 10.1073/pnas.81.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jelinek W. R., Toomey T. P., Leinwand L., Duncan C. H., Biro P. A., Choudary P. V., Weissman S. M., Rubin C. M., Houck C. M., Deininger P. L. Ubiquitous, interspersed repeated sequences in mammalian genomes. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1398–1402. doi: 10.1073/pnas.77.3.1398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kern F. G., Basilico C. Transcription from the polyoma late promoter in cells stably transformed by chimeric plasmids. Mol Cell Biol. 1985 Apr;5(4):797–807. doi: 10.1128/mcb.5.4.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McNutt N. S., Fletcher V., Conant M. A. Early lesions of Kaposi's sarcoma in homosexual men. An ultrastructural comparison with other vascular proliferations in skin. Am J Pathol. 1983 Apr;111(1):62–77. [PMC free article] [PubMed] [Google Scholar]
  17. Okayama H., Berg P. High-efficiency cloning of full-length cDNA. Mol Cell Biol. 1982 Feb;2(2):161–170. doi: 10.1128/mcb.2.2.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pellegrini S., Dailey L., Basilico C. Amplification and excision of integrated polyoma DNA sequences require a functional origin of replication. Cell. 1984 Apr;36(4):943–949. doi: 10.1016/0092-8674(84)90044-8. [DOI] [PubMed] [Google Scholar]
  19. Roussel M. F., Sherr C. J., Barker P. E., Ruddle F. H. Molecular cloning of the c-fms locus and its assignment to human chromosome 5. J Virol. 1983 Dec;48(3):770–773. doi: 10.1128/jvi.48.3.770-773.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  21. Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
  22. Takahashi M., Ritz J., Cooper G. M. Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell. 1985 Sep;42(2):581–588. doi: 10.1016/0092-8674(85)90115-1. [DOI] [PubMed] [Google Scholar]
  23. Wigler M., Pellicer A., Silverstein S., Axel R., Urlaub G., Chasin L. DNA-mediated transfer of the adenine phosphoribosyltransferase locus into mammalian cells. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1373–1376. doi: 10.1073/pnas.76.3.1373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Xu D. Q., Guilhot S., Galibert F. Restriction fragment length polymorphism of the human c-fms gene. Proc Natl Acad Sci U S A. 1985 May;82(9):2862–2865. doi: 10.1073/pnas.82.9.2862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Young D., Waitches G., Birchmeier C., Fasano O., Wigler M. Isolation and characterization of a new cellular oncogene encoding a protein with multiple potential transmembrane domains. Cell. 1986 Jun 6;45(5):711–719. doi: 10.1016/0092-8674(86)90785-3. [DOI] [PubMed] [Google Scholar]

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