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. 1987 Jul 24;15(14):5669–5680. doi: 10.1093/nar/15.14.5669

Concurrent mutations in two different ras genes in acute myelocytic leukemias.

J W Janssen, J Lyons, A C Steenvoorden, H Seliger, C R Bartram
PMCID: PMC306014  PMID: 3475676

Abstract

DNA transfection analyses (tumorigenicity assay) and hybridization to mutation specific oligonucleotide probes established point mutations in codon 61 of both, N-ras and Ki-ras genes in fresh leukemic cells of an AML patient. Concurrent activation of N-ras and Ki-ras sequences by point mutations in codons 12 were demonstrated for AML cell line Rc2a. Moreover, using a rapid and sensitive dot-blot screening procedure based on the combination of in vitro amplification of ras specific sequences and oligonucleotide hybridization we could show that ras gene activation was not present in primary leukemic cells of the patient this cell line had been derived from, but rather occurred during later passages of Rc2a.

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Selected References

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  1. Bos J. L., Toksoz D., Marshall C. J., Verlaan-de Vries M., Veeneman G. H., van der Eb A. J., van Boom J. H., Janssen J. W., Steenvoorden A. C. Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia. 1985 Jun 27-Jul 3Nature. 315(6022):726–730. doi: 10.1038/315726a0. [DOI] [PubMed] [Google Scholar]
  2. Bos J. L., Verlaan-de Vries M., Jansen A. M., Veeneman G. H., van Boom J. H., van der Eb A. J. Three different mutations in codon 61 of the human N-ras gene detected by synthetic oligonucleotide hybridization. Nucleic Acids Res. 1984 Dec 11;12(23):9155–9163. doi: 10.1093/nar/12.23.9155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bos J. L., Verlaan-de Vries M., Marshall C. J., Veeneman G. H., van Boom J. H., van der Eb A. J. A human gastric carcinoma contains a single mutated and an amplified normal allele of the Ki-ras oncogene. Nucleic Acids Res. 1986 Feb 11;14(3):1209–1217. doi: 10.1093/nar/14.3.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bos J. L., Verlaan-de Vries M., van der Eb A. J., Janssen J. W., Delwel R., Löwenberg B., Colly L. P. Mutations in N-ras predominate in acute myeloid leukemia. Blood. 1987 Apr;69(4):1237–1241. [PubMed] [Google Scholar]
  5. Bradley T. R., Pilkington G., Garson M., Hodgson G. S., Kraft N. Cell lines derived from a human myelomonocytic leukaemia. Br J Haematol. 1982 Aug;51(4):595–604. doi: 10.1111/j.1365-2141.1982.tb02823.x. [DOI] [PubMed] [Google Scholar]
  6. Chang E. H., Furth M. E., Scolnick E. M., Lowy D. R. Tumorigenic transformation of mammalian cells induced by a normal human gene homologous to the oncogene of Harvey murine sarcoma virus. Nature. 1982 Jun 10;297(5866):479–483. doi: 10.1038/297479a0. [DOI] [PubMed] [Google Scholar]
  7. Cooper G. M. Cellular transforming genes. Science. 1982 Aug 27;217(4562):801–806. doi: 10.1126/science.6285471. [DOI] [PubMed] [Google Scholar]
  8. Der C. J., Finkel T., Cooper G. M. Biological and biochemical properties of human rasH genes mutated at codon 61. Cell. 1986 Jan 17;44(1):167–176. doi: 10.1016/0092-8674(86)90495-2. [DOI] [PubMed] [Google Scholar]
  9. Ellis R. W., Defeo D., Shih T. Y., Gonda M. A., Young H. A., Tsuchida N., Lowy D. R., Scolnick E. M. The p21 src genes of Harvey and Kirsten sarcoma viruses originate from divergent members of a family of normal vertebrate genes. Nature. 1981 Aug 6;292(5823):506–511. doi: 10.1038/292506a0. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Fasano O., Taparowsky E., Fiddes J., Wigler M., Goldfarb M. Sequence and structure of the coding region of the human H-ras-1 gene from T24 bladder carcinoma cells. J Mol Appl Genet. 1983;2(2):173–180. [PubMed] [Google Scholar]
  12. Gibbs J. B., Sigal I. S., Poe M., Scolnick E. M. Intrinsic GTPase activity distinguishes normal and oncogenic ras p21 molecules. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5704–5708. doi: 10.1073/pnas.81.18.5704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Gorman C., Padmanabhan R., Howard B. H. High efficiency DNA-mediated transformation of primate cells. Science. 1983 Aug 5;221(4610):551–553. doi: 10.1126/science.6306768. [DOI] [PubMed] [Google Scholar]
  15. Hall A., Brown R. Human N-ras: cDNA cloning and gene structure. Nucleic Acids Res. 1985 Jul 25;13(14):5255–5268. doi: 10.1093/nar/13.14.5255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hall A., Marshall C. J., Spurr N. K., Weiss R. A. Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1. Nature. 1983 Jun 2;303(5916):396–400. doi: 10.1038/303396a0. [DOI] [PubMed] [Google Scholar]
  17. Janssen J. W., Steenvoorden A. C., Collard J. G., Nusse R. Oncogene activation in human myeloid leukemia. Cancer Res. 1985 Jul;45(7):3262–3267. [PubMed] [Google Scholar]
  18. Lacal J. C., Aaronson S. A. Activation of ras p21 transforming properties associated with an increase in the release rate of bound guanine nucleotide. Mol Cell Biol. 1986 Dec;6(12):4214–4220. doi: 10.1128/mcb.6.12.4214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lacal J. C., Srivastava S. K., Anderson P. S., Aaronson S. A. Ras p21 proteins with high or low GTPase activity can efficiently transform NIH/3T3 cells. Cell. 1986 Feb 28;44(4):609–617. doi: 10.1016/0092-8674(86)90270-9. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. McCoy M. S., Toole J. J., Cunningham J. M., Chang E. H., Lowy D. R., Weinberg R. A. Characterization of a human colon/lung carcinoma oncogene. Nature. 1983 Mar 3;302(5903):79–81. doi: 10.1038/302079a0. [DOI] [PubMed] [Google Scholar]
  22. McGrath J. P., Capon D. J., Goeddel D. V., Levinson A. D. Comparative biochemical properties of normal and activated human ras p21 protein. Nature. 1984 Aug 23;310(5979):644–649. doi: 10.1038/310644a0. [DOI] [PubMed] [Google Scholar]
  23. McGrath J. P., Capon D. J., Goeddel D. V., Levinson A. D. Comparative biochemical properties of normal and activated human ras p21 protein. Nature. 1984 Aug 23;310(5979):644–649. doi: 10.1038/310644a0. [DOI] [PubMed] [Google Scholar]
  24. McGrath J. P., Capon D. J., Smith D. H., Chen E. Y., Seeburg P. H., Goeddel D. V., Levinson A. D. Structure and organization of the human Ki-ras proto-oncogene and a related processed pseudogene. Nature. 1983 Aug 11;304(5926):501–506. doi: 10.1038/304501a0. [DOI] [PubMed] [Google Scholar]
  25. McKay I. A., Marshall C. J., Calés C., Hall A. Transformation and stimulation of DNA synthesis in NIH-3T3 cells are a titratable function of normal p21N-ras expression. EMBO J. 1986 Oct;5(10):2617–2621. doi: 10.1002/j.1460-2075.1986.tb04542.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Murray M. J., Cunningham J. M., Parada L. F., Dautry F., Lebowitz P., Weinberg R. A. The HL-60 transforming sequence: a ras oncogene coexisting with altered myc genes in hematopoietic tumors. Cell. 1983 Jul;33(3):749–757. doi: 10.1016/0092-8674(83)90017-x. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Pulciani S., Santos E., Long L. K., Sorrentino V., Barbacid M. ras gene Amplification and malignant transformation. Mol Cell Biol. 1985 Oct;5(10):2836–2841. doi: 10.1128/mcb.5.10.2836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Saiki R. K., Bugawan T. L., Horn G. T., Mullis K. B., Erlich H. A. Analysis of enzymatically amplified beta-globin and HLA-DQ alpha DNA with allele-specific oligonucleotide probes. Nature. 1986 Nov 13;324(6093):163–166. doi: 10.1038/324163a0. [DOI] [PubMed] [Google Scholar]
  30. Sekiya T., Fushimi M., Hori H., Hirohashi S., Nishimura S., Sugimura T. Molecular cloning and the total nucleotide sequence of the human c-Ha-ras-1 gene activated in a melanoma from a Japanese patient. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4771–4775. doi: 10.1073/pnas.81.15.4771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Taparowsky E., Shimizu K., Goldfarb M., Wigler M. Structure and activation of the human N-ras gene. Cell. 1983 Sep;34(2):581–586. doi: 10.1016/0092-8674(83)90390-2. [DOI] [PubMed] [Google Scholar]
  32. Taya Y., Hosogai K., Hirohashi S., Shimosato Y., Tsuchiya R., Tsuchida N., Fushimi M., Sekiya T., Nishimura S. A novel combination of K-ras and myc amplification accompanied by point mutational activation of K-ras in a human lung cancer. EMBO J. 1984 Dec 1;3(12):2943–2946. doi: 10.1002/j.1460-2075.1984.tb02236.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Verlaan-de Vries M., Bogaard M. E., van den Elst H., van Boom J. H., van der Eb A. J., Bos J. L. A dot-blot screening procedure for mutated ras oncogenes using synthetic oligodeoxynucleotides. Gene. 1986;50(1-3):313–320. doi: 10.1016/0378-1119(86)90335-5. [DOI] [PubMed] [Google Scholar]
  35. Yamada H., Yoshida T., Sakamoto H., Terada M., Sugimura T. Establishment of a human pancreatic adenocarcinoma cell line (PSN-1) with amplifications of both c-myc and activated c-Ki-ras by a point mutation. Biochem Biophys Res Commun. 1986 Oct 15;140(1):167–173. doi: 10.1016/0006-291x(86)91072-7. [DOI] [PubMed] [Google Scholar]

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