Skip to main content
NCBI home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1990 Jan;81(1):22–27. doi: 10.1111/j.1349-7006.1990.tb02502.x

Point Mutations of c‐ras Genes in Human Bladder Cancer and Kidney Cancer

Yasuhiko Nagata 1, Masumi Abe 2, Kohmei Kobayashi 3, Shigeru Saiki 4, Toshihiko Kotake 4, Kazuhiro Yoshikawa 5, Ryuzo Ueda 6, Eiichi Nakayama 1, Hiroshi Shiku 1,✉
PMCID: PMC5917946  PMID: 2108944

ABSTRACT

Point mutations of c‐ras genes at codons 12, 13 and 61 were analyzed in 26 cases of bladder cancer and 16 cases of kidney cancer. DNA prepared from either frozen tissues or 10% formalin‐fixed, paraffin‐embedded tissues were amplified by means of polymerase chain reaction methods, and mutations were analyzed by dot blot hybridization assays with oligonucleotide probes. In three cases of bladder cancer c‐ras mutations were found, at codons 13 and 61 of c‐Ha‐ras and at codon 61 of c‐Ki‐ras, while no mutation was found in kidney cancer. No mutation was found in normal bladder epithelial tissues from the same patients. Our findings, taken together, may indicate relative scarcity of c‐ras mutations in these types of human cancer. The results of dot blot hybridization assays and DNA sequencing showed a G‐to‐C transition of the first nucleotide at codon 13 of c‐Ha‐ras. This is the first time that such a point mutation has been detected in human cancer tissues.

Keywords: c‐ras, Point mutation, Polymerase chain reaction, Bladder cancer, Kidney cancer

Full Text

The Full Text of this article is available as a PDF (316.4 KB).

REFERENCES

  • 1. ) Barbacid , M.ras genes . Ann. Rev. Biochem. , 56 , 779 – 827 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Fasano , O. , Aldrich , T. , Tamanoi , F. , Taparowsky , E. , Furth , M. and Wigler , M.Analysis of the transforming potential of the human H‐ras gene by random mutagenesis . Proc. Natl. Acad. Sci. USA , 81 , 4008 – 4012 ( 1984. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. ) Walter , M. , Clark , S. G. and Levinson , A. D.The oncogenic activation of human p21 ras by a novel mechanism . Science , 233 , 649 – 652 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Sigal , I. S. , Gibbs , J. B. , D'Alonzo , J. S. , Temeles , G. L. , Wolanski , B. S. , Socher , S. H. and Scolnick , E. M.Mutant ras‐encoded proteins with altered nucleotide binding exert dominant biological effects . Proc. Natl. Acad. Sci. USA , 83 , 952 – 956 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. ) Bos , J. L.The ras gene family and human carcinogenesis . Mutat. Res. , 195 , 255 – 271 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Bos , J. L. , Fearon , E. R. , Hamilton , S. R. , Verlaan‐de Vries , M. , van Boom , J. H. , van der Eb , A. J. and Vogelstein , B.Prevalence of ras gene mutations in human colorectal cancers . Nature , 327 , 293 – 297 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Forrester , K. , Almoguera , C. , Han , K. , Grizzle , W. E. and Perucho , M.Detection of high incidence of K‐ras oncogenes during human colon tumorigenesis . Nature , 327 , 298 – 303 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Almoguera , C. , Shibata , D. , Forrester , K. , Martin , J. , Arnheim , N. and Perucho , M.Most human carcinomas of the exocrine pancreas contain mutant c‐K‐ras genes . Cell , 53 , 549 – 554 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Smit , V. T. H. B. , Boot , A. J. M. , Smits , A. M. M. , Fleuren , C. J. , Cornelisse , C. J. and Bos , J. L.K RAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas . Nucleic Acids Res. , 16 , 7773 – 7782 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. ) Rodenhuis , S. , van de Wetering , M. L. , Mooi , W. J. , Evers , S. G. , van Zandwijk , N. and Bos , J. L.Mutational activation of the K‐ras oncogene, a possible pathogenetic factor in adenocarcinoma of the lung . N. Engl. J. Med. , 317 , 929 – 935 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) van't Veer , L. J. , Hermens , R. , van den Berg‐Bakker , L. A. M. , Cheng , N. C. , Fleuren , G‐J. , Bos , J. L. , Cleton , F. J. and Schrier , P. I.ras oncogene activation in human ovarian carcinoma . Oncogene , 2 , 157 – 165 ( 1988. ). [PubMed] [Google Scholar]
  • 12. ) Tsuda , H. , Hirohashi , S. , Shimosato , Y. , Ino , Y. , Yoshida , T. and Terada , M.Low incidence of point mutation of c‐Ki‐ras and N‐ras oncogenes in human hepatocellular carcinoma . Jpn. J. Cancer Res. , 80 , 196 – 199 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. ) Hollstein , M. C. , Smits , A. M. , Galiana , C. , Yamasaki , H. , Bos , J. L. , Mandard , A. , Partensky , C. and Montesano , R.Amplification of epidermal growth factor receptor gene but no evidence of ras mutations in primary human esophageal cancers . Cancer Res. , 48 , 5119 – 5123 ( 1988. ). [PubMed] [Google Scholar]
  • 14. ) Rochlitz , C. F. , Scott , G. K. , Dodson , J. M. , Liu , E. , Dollbaum , C. , Smith , H. S. and Benz , C. C.Incidence of activating ras oncogene mutations associated with primary and metastatic human breast cancer . Cancer Res. , 49 , 357 – 360 ( 1989. ). [PubMed] [Google Scholar]
  • 15. ) Hamatani , K. , Nagata , Y. , Abe , M. , Abe , K. , Toki , H. , Ikeda , S. , Nakayama , E. and Shiku , H.Increased expression of ras genes in non‐Hodgkin's lymphomas is not associated with oncogenic activation of those genes by point mutation . Jpn. J. Cancer Res. , 80 , 706 – 710 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. ) Neri , A. , Knowles , D. M. , Greco , A. , McCormick , F. and Dalla‐Favera , R.Analysis of RAS oncogene mutations in human lymphoid malignancies . Proc. Natl. Acad. Sci. USA , 85 , 9268 – 9272 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. ) Blin , N. and Stafford , D. W.General method for isolation of high molecular weight DNA from eukaryotes . Nucleic Acids Res. , 3 , 2303 – 2308 ( 1976. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. ) Shibata , D. K. , Arnheim , N. and Martin , W. J.Detection of human papilloma virus in paraffin‐embedded tissue using the polymerase chain reaction . J. Exp. Med. , 167 , 225 – 230 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. ) Verlaan‐de Vries , M. , Bogaard , M. E. , van den Elst , H. , van Boom , J. H. , van der Eb , A. J. and Bos , J. L.A dot‐blot screening procedure for mutated ras oncogenes using synthetic oligodeoxynucleotides . Gene , 50 , 313 – 320 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Saiki , R. K. , Scharf , S. , Faloona , F. , Mullis , K. B. , Horn , G. T. , Erlich , H. A. and Arnheim , N.Enzymatic amplification of β‐globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia . Science , 230 , 1350 – 1354 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Mullis , K. B. and Faloona , F. A.Specific synthesis of DNA in vitro via a polymerase‐catalyzed chain reaction . Methods Enzymol. , 155 , 335 – 350 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Sanger , F.Determination of nucleotide sequences in DNA . Science , 214 , 1205 – 1210 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Fujita , J. , Srivastava , S. K. , Kraus , M. H. , Rhim , J. S. , Tronick , S. R. and Aaronson , S. A.Frequency of molecular alterations affecting ras protooncogenes in human urinary tract tumors . Proc. Natl. Acad. Sci. USA , 82 , 3849 – 3853 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. ) Fujita , J. , Kraus , M. H. , Onoue , H. , Srivastava , S. K. , Ebi , Y. , Kitamura , Y. and Rhim , J. S.Activated H‐ras oncogenes in human kidney tumors . Cancer Res. , 48 , 5251 – 5255 ( 1988. ). [PubMed] [Google Scholar]
  • 25. ) Bos , J. L. , Verlaan‐de Vries , M. , van der Eb , A. J. , Janssen , J. W. G. , Delwel , R. , Löwenberg , B. and Colly , L. P.Mutations in N‐ras predominate in acute myeloid leukemia . Blood , 69 , 1237 – 1241 ( 1987. ). [PubMed] [Google Scholar]
  • 26. ) Reynolds , S. H. , Stowers , S. J. , Patterson , R. M. , Maronpot , R. R. , Aaronson , S. A. and Anderson , M. W.Activated oncogenes in B6C3F1 mouse liver tumors: implications for risk assessment . Science , 237 , 1309 – 1316 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 27. ) Tadokoro , K. , Ueda , M. , Ohshima , T. , Fujita , K. , Rikimaru , K. , Takahashi , N. , Enomoto , S , and Tsuchida , N.Activation of oncogenes in human oral cancer cells: a novel codon 13 mutation of c‐H‐ras‐1 and concurrent amplifications of c‐erbB‐1 and c‐myc. Oncogene , 4 , 499 – 505 ( 1989. ). [PubMed] [Google Scholar]
  • 28. ) Nagata , Y. , Abe , M. , Kobayashi , K. , Yoshida , K. , Ishibashi , T. , Naoe , T. , Nakayama , E. and Shiku , H.Glycine to aspartic acid mutations at codon 13 of c‐Ki‐ras gene in human gastro‐intestinal cancers . Cancer Res. , 50 ( 1990. ), in press . [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES