Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Mutations of the E–cadherin gene in human gynecologic cancers

Abstract

Expression of the E–cadherin cell adhesion molecule is reduced in several types of human carcinomas, and the protein serves as an invasion suppressor in vitro. To determine if mutations of the E–cadherin gene (on chromosome 16q22) contribute to epithelial tumorigenesis, 135 carcinomas of the endometrium and ovary were examined for alterations in the E–cadherin coding region. Four mutations were identified: one somatic nonsense and one somatic missense mutation, both with retention of the wild–type alleles, and two missense mutations with somatic loss of heterozygosity in the tumour tissue. These data support the classification of E–cadherin as a human tumour suppressor gene.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Fearon, E.R. et al. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 247, 49–56 (1990).

    Article  CAS  PubMed  Google Scholar 

  2. Höhne, M.W., Halatsch, M.-E., Kahl, G.F. & Weinel, R.J. Frequent loss of expression of the potential tumor suppressor gene DCC in ductal pancreatic adenocarcinoma. Cancer Res. 52, 2616–2619 (1992).

    PubMed  Google Scholar 

  3. Gao, X., Honn, K.V., Grignon, D., Sakr, W. & Chen, Y.Q. Frequent loss of expression and loss of heterozygosity of the putative tumor suppressor gene DCC in prostatic carcinoma. Cancer Res. 53, 2723–2727 (1993).

    CAS  PubMed  Google Scholar 

  4. Edelman, G.M. Morphoregulatory molecules. Biochemistry 27, 3533–3543 (1988).

    Article  CAS  PubMed  Google Scholar 

  5. Takeichi, M. Cadherins: a molecular family important in selective cell-cell adhesion. Annu. Rev. Biochem. 59, 237–252 (1990).

    Article  CAS  PubMed  Google Scholar 

  6. Mahoney, P.A. et al. The fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene superfamily. Cell 67, 853–868 (1991).

    Article  CAS  PubMed  Google Scholar 

  7. Shimoyama, Y. et al. Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas. Cancer Res. 49, 2128–2133 (1989).

    CAS  PubMed  Google Scholar 

  8. Nagafuchi, A., Shirayoshi, Y., Okazaki, K., Yasuda, K. & Takeichi, M. Transformation of cell adhesion properties by exogenously introduced E-cadherin cDNA. Nature 329, 341–343 (1987).

    Article  CAS  PubMed  Google Scholar 

  9. Behrens, J., Mareel, M.M., Van Roy, F.M. & Birchmeier, W. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J. Cell Biol. 108, 2435–2447 (1989).

    Article  CAS  PubMed  Google Scholar 

  10. Frixen, U.H. et al. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J. Cell Biol. 113, 173–185 (1991).

    Article  CAS  PubMed  Google Scholar 

  11. Vleminckx, K., Vakaet, L., Mareel, M., Fiers, W. & Van Roy, F. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell 66, 107–119 (1991).

    Article  CAS  PubMed  Google Scholar 

  12. Shimoyama, Y. & Hirohashi, S. Expression of E- and P-cadherin in gastric carcinomas. Cancer Res. 51, 2185–2192 (1991).

    CAS  PubMed  Google Scholar 

  13. Bussemakers, M.J.G. et al. Decreased expression of E-cadherin in the progression of rat prostatic cancer. Cancer Res. 52, 2916–2922 (1992).

    CAS  PubMed  Google Scholar 

  14. Umbas, R. et al. Expression of the cellular adhesion molecule E-cadherin Is reduced or absent in high-grade prostate cancer. Cancer Res. 52, 5104–5109 (1992).

    CAS  PubMed  Google Scholar 

  15. Brabant, G. et al. E-Cadherin: A differentiation marker in thyroid malignancies. Cancer Res. 53, 4987–4993 (1993).

    CAS  PubMed  Google Scholar 

  16. Bringuier, P.P. et al. Decreased E-cadherin immunoreactivity correlates with poor survival in patients with bladder tumors. Cancer Res. 53, 3241–3245 (1993).

    CAS  PubMed  Google Scholar 

  17. Inoue, M., Ogawa, H., Miyata, M., Shiozaki, H. & Tanizawa, O. Expression of E-cadherin in normal, benign, and malignant tissues of female genital organs. Am. J. clin. Pathol. 98, 76–80 (1992).

    Article  CAS  PubMed  Google Scholar 

  18. Mansouri, A., Spurr, N., Goodfellow, P.N. & Kemler, R. Characterization and chromosomal localization of the gene encoding the human cell adhesion molecule uvomorulin. Differentiation 38, 67–71 (1988).

    Article  CAS  PubMed  Google Scholar 

  19. Natt, E., Magenis, R.E., Zimmer, J., Mansouri, A. & Scherer, G. Regional assignment of the human loci for uvomorulin (UVO) and chymotrypsinogen B (CTRB) with the help of two overlapping deletions on the long arm of chromosome 16. Cytogonet. Cell Genet. 50, 145–148 (1989).

    Article  CAS  Google Scholar 

  20. Carter, B.S. et al. Allelic loss of chromosomes 16q and 10q in human prostate cancer. Proc. natn. Acad. Sci. U.S.A. 87, 8751–8755 (1990).

    Article  CAS  Google Scholar 

  21. Bergerheim, U.S.R., Kunimi, K., Collins, V.P. & Ekman, P. Deletion mapping of chromosomes 8,10, and 16 in human prostatic carcinoma. Genes Chrom. Cancer 3, 215–220 (1991).

    Article  CAS  PubMed  Google Scholar 

  22. Kunimi, K., Bergerheim, U.S.R., Larsson, I.-L., Ekman, P. & Collins, V.P. Allelotyping of human prostatic adenocarcinoma. Genomics 11, 530–536 (1991).

    Article  CAS  PubMed  Google Scholar 

  23. Sato, T., Saito, H., Morita, R., Koi, S., Lee, J.-H. & Nakamura, Y. Allelotype of human ovarian cancer. Cancer Res. 51, 5118–5122 (1991).

    CAS  PubMed  Google Scholar 

  24. Devilee, P. et al. Allelotype of human breast carcinoma: a second major site for loss of heterozygosity is on chromosome 6q. Oncogene 6, 1705–1711 (1991).

    CAS  PubMed  Google Scholar 

  25. Tsuda, H. et al. Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma. Proc. natn. Acad. Sci. U.S.A. 87, 6791–6794 (1990).

    Article  CAS  Google Scholar 

  26. Bussemakers, M.J.G., Mees, S.G.M., Van Bokhoven, A., Debruyne, F.M.J. & Schalken, J.A. Molecular cloning and characterization of the human E-cadherin cDNA. Molec. Biol. Rep. 17, 123–128 (1993).

    Article  CAS  Google Scholar 

  27. Oda, T. et al. E-cadherin gene mutations in human gastric carcinoma cell lines. Proc. natn. Acad. Sci. U.S.A. 91, 1858–1862 (1994).

    Article  CAS  Google Scholar 

  28. Hoffman, S. & Edelman, G.M. Kinetics of homophilic binding by E and A forms of the neural cell adhesion molecule. Proc. natn. Acad. Sci. U.S.A. 80, 5762–5766 (1983).

    Article  CAS  Google Scholar 

  29. Doherty, P. et al. A threshold effect of the major isoforms of NCAM on neurite outgrowth. Nature 343, 464–466 (1990).

    Article  CAS  PubMed  Google Scholar 

  30. Sasaki et al. Mutation of the Ki-ras protooncogene in human endometrial hyperplasia and carcinoma. Cancer Res. 53, 1906–1910 (1993).

    CAS  PubMed  Google Scholar 

  31. Chomczynski, P. & Sacchi, N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenot-chloroform extraction. Anal. Biochem. 162, 156–159 (1983).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Risinger, J., Berchuck, A., Kohler, M. et al. Mutations of the E–cadherin gene in human gynecologic cancers. Nat Genet 7, 98–102 (1994). https://doi.org/10.1038/ng0594-98

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0594-98

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing