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. 1986 Feb 11;14(3):1209–1217. doi: 10.1093/nar/14.3.1209

A human gastric carcinoma contains a single mutated and an amplified normal allele of the Ki-ras oncogene.

J L Bos, M Verlaan-de Vries, C J Marshall, G H Veeneman, J H van Boom, A J van der Eb
PMCID: PMC339498  PMID: 3951985

Abstract

The DNA from various human tumors and tumor cell lines was screened for the presence of mutated ras oncogenes with synthetic oligonucleotide probes, as well as with the NIH/3T3 cell transfection assay. Among the various mutations found we discovered two novel Ki-ras mutations in codon 12: gly to ala and gly to ser. A gastric carcinoma was found to possess a single mutated Ki-ras allele (gly-12 to ser), as well as a 30-50 fold amplified normal allele. This implies that two activating steps must have occurred in this malignancy.

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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. Capon D. J., Seeburg P. H., McGrath J. P., Hayflick J. S., Edman U., Levinson A. D., Goeddel D. V. Activation of Ki-ras2 gene in human colon and lung carcinomas by two different point mutations. Nature. 1983 Aug 11;304(5926):507–513. doi: 10.1038/304507a0. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Chipperfield R. G., Jones S. S., Lo K. M., Weinberg R. A. Activation of Ha-ras p21 by substitution, deletion, and insertion mutations. Mol Cell Biol. 1985 Aug;5(8):1809–1813. doi: 10.1128/mcb.5.8.1809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cooper G. M. Cellular transforming genes. Science. 1982 Aug 27;217(4562):801–806. doi: 10.1126/science.6285471. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Fasano O., Aldrich T., Tamanoi F., Taparowsky E., Furth M., Wigler M. Analysis of the transforming potential of the human H-ras gene by random mutagenesis. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4008–4012. doi: 10.1073/pnas.81.13.4008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. 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]
  12. Leibovitz A., Stinson J. C., McCombs W. B., 3rd, McCoy C. E., Mazur K. C., Mabry N. D. Classification of human colorectal adenocarcinoma cell lines. Cancer Res. 1976 Dec;36(12):4562–4569. [PubMed] [Google Scholar]
  13. Marshall C. J., Hall A., Weiss R. A. A transforming gene present in human sarcoma cell lines. Nature. 1982 Sep 9;299(5879):171–173. doi: 10.1038/299171a0. [DOI] [PubMed] [Google Scholar]
  14. McCoy M. S., Bargmann C. I., Weinberg R. A. Human colon carcinoma Ki-ras2 oncogene and its corresponding proto-oncogene. Mol Cell Biol. 1984 Aug;4(8):1577–1582. doi: 10.1128/mcb.4.8.1577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Melchior W. B., Jr, Von Hippel P. H. Alteration of the relative stability of dA-dT and dG-dC base pairs in DNA. Proc Natl Acad Sci U S A. 1973 Feb;70(2):298–302. doi: 10.1073/pnas.70.2.298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Santos E., Martin-Zanca D., Reddy E. P., Pierotti M. A., Della Porta G., Barbacid M. Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient. Science. 1984 Feb 17;223(4637):661–664. doi: 10.1126/science.6695174. [DOI] [PubMed] [Google Scholar]
  19. Sweet R. W., Yokoyama S., Kamata T., Feramisco J. R., Rosenberg M., Gross M. The product of ras is a GTPase and the T24 oncogenic mutant is deficient in this activity. Nature. 1984 Sep 20;311(5983):273–275. doi: 10.1038/311273a0. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Weinberg R. A. ras Oncogenes and the molecular mechanisms of carcinogenesis. Blood. 1984 Dec;64(6):1143–1145. [PubMed] [Google Scholar]
  23. Wood W. I., Gitschier J., Lasky L. A., Lawn R. M. Base composition-independent hybridization in tetramethylammonium chloride: a method for oligonucleotide screening of highly complex gene libraries. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1585–1588. doi: 10.1073/pnas.82.6.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]

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