Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1990 Aug;62(2):226–230. doi: 10.1038/bjc.1990.265

Alterations of oncogenes in metastatic tumours of human gastric carcinomas.

T Tsujino 1, K Yoshida 1, H Nakayama 1, H Ito 1, T Shimosato 1, E Tahara 1
PMCID: PMC1971835  PMID: 2386738

Abstract

To determine whether alterations in oncogenes are associated with tumour progression and metastasis, DNAs from 32 metastatic tumour samples of different sites in 12 autopsy cases of gastric carcinomas were analysed for alterations of ERBB, ERBB2, HST1, INT2 and LMYC genes by Southern blot hybridisation. DNAs from 89 primary gastric carcinomas including 69 advanced carcinomas and 20 early carcinomas were also examined. In primary tumours, no amplification was detected in early carcinomas, while amplification of ERBB and ERBB2 genes was detected in one (1.4%) and four (5.8%) out of 69 advanced carcinomas, respectively. In metastatic tumours, amplification of ERBB gene was detected in three metastatic tumours (9.4%), and all of them had allelic deletion of the LMYC gene. Regardless of histological type, amplification of ERBB2 gene was detected in 8 metastatic tumours (25.0%), out of which three tumours had coamplification of HST1 and INT2 genes. The incidence of ERBB2 amplification in metastatic tumours was significantly higher than that in primary tumours. These results indicate that multi-alterations in oncogenes might occur during tumour progression and metastasis of human gastric carcinomas.

Full text

PDF
226

Images in this article

227Figure 1
on p.227
228Figure 2
on p.228
228Figure 3
on p.228
228Figure 4
on p.228

Selected References

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

  1. Baker S. J., Fearon E. R., Nigro J. M., Hamilton S. R., Preisinger A. C., Jessup J. M., vanTuinen P., Ledbetter D. H., Barker D. F., Nakamura Y. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science. 1989 Apr 14;244(4901):217–221. doi: 10.1126/science.2649981. [DOI] [PubMed] [Google Scholar]
  2. Barbacid M. ras genes. Annu Rev Biochem. 1987;56:779–827. doi: 10.1146/annurev.bi.56.070187.004023. [DOI] [PubMed] [Google Scholar]
  3. Di Marco E., Pierce J. H., Fleming T. P., Kraus M. H., Molloy C. J., Aaronson S. A., Di Fiore P. P. Autocrine interaction between TGF alpha and the EGF-receptor: quantitative requirements for induction of the malignant phenotype. Oncogene. 1989 Jul;4(7):831–838. [PubMed] [Google Scholar]
  4. Dubeau L., Chandler L. A., Gralow J. R., Nichols P. W., Jones P. A. Southern blot analysis of DNA extracted from formalin-fixed pathology specimens. Cancer Res. 1986 Jun;46(6):2964–2969. [PubMed] [Google Scholar]
  5. Fey M. F., Hesketh C., Wainscoat J. S., Gendler S., Thein S. L. Clonal allele loss in gastrointestinal cancers. Br J Cancer. 1989 May;59(5):750–754. doi: 10.1038/bjc.1989.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Forrester K., Almoguera C., Han K., Grizzle W. E., Perucho M. Detection of high incidence of K-ras oncogenes during human colon tumorigenesis. 1987 May 28-Jun 3Nature. 327(6120):298–303. doi: 10.1038/327298a0. [DOI] [PubMed] [Google Scholar]
  7. Goelz S. E., Hamilton S. R., Vogelstein B. Purification of DNA from formaldehyde fixed and paraffin embedded human tissue. Biochem Biophys Res Commun. 1985 Jul 16;130(1):118–126. doi: 10.1016/0006-291x(85)90390-0. [DOI] [PubMed] [Google Scholar]
  8. Green A. R. Recessive mechanisms of malignancy. Br J Cancer. 1988 Aug;58(2):115–121. doi: 10.1038/bjc.1988.176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Johnson B. E., Makuch R. W., Simmons A. D., Gazdar A. F., Burch D., Cashell A. W. myc family DNA amplification in small cell lung cancer patients' tumors and corresponding cell lines. Cancer Res. 1988 Sep 15;48(18):5163–5166. [PubMed] [Google Scholar]
  10. 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]
  11. Lee J. H., Kavanagh J. J., Wharton J. T., Wildrick D. M., Blick M. Allele loss at the c-Ha-ras1 locus in human ovarian cancer. Cancer Res. 1989 Mar 1;49(5):1220–1222. [PubMed] [Google Scholar]
  12. Mathew C. G., Smith B. A., Thorpe K., Wong Z., Royle N. J., Jeffreys A. J., Ponder B. A. Deletion of genes on chromosome 1 in endocrine neoplasia. Nature. 1987 Aug 6;328(6130):524–526. doi: 10.1038/328524a0. [DOI] [PubMed] [Google Scholar]
  13. Nicolson G. L. Tumor cell instability, diversification, and progression to the metastatic phenotype: from oncogene to oncofetal expression. Cancer Res. 1987 Mar 15;47(6):1473–1487. [PubMed] [Google Scholar]
  14. Sakamoto H., Mori M., Taira M., Yoshida T., Matsukawa S., Shimizu K., Sekiguchi M., Terada M., Sugimura T. Transforming gene from human stomach cancers and a noncancerous portion of stomach mucosa. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3997–4001. doi: 10.1073/pnas.83.11.3997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Slamon D. J., Clark G. M., Wong S. G., Levin W. J., Ullrich A., McGuire W. L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177–182. doi: 10.1126/science.3798106. [DOI] [PubMed] [Google Scholar]
  16. Smit V. T., Boot A. J., Smits A. M., Fleuren G. J., Cornelisse C. J., Bos J. L. KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas. Nucleic Acids Res. 1988 Aug 25;16(16):7773–7782. doi: 10.1093/nar/16.16.7773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Tahara E., Sumiyoshi H., Hata J., Yasui W., Taniyama K., Hayashi T., Nagae S., Sakamoto S. Human epidermal growth factor in gastric carcinoma as a biologic marker of high malignancy. Jpn J Cancer Res. 1986 Feb;77(2):145–152. [PubMed] [Google Scholar]
  19. Tsuda H., Shimosato Y., Upton M. P., Yokota J., Terada M., Ohira M., Sugimura T., Hirohashi S. Retrospective study on amplification of N-myc and c-myc genes in pediatric solid tumors and its association with prognosis and tumor differentiation. Lab Invest. 1988 Sep;59(3):321–327. [PubMed] [Google Scholar]
  20. Tsuda T., Nakatani H., Matsumura T., Yoshida K., Tahara E., Nishihira T., Sakamoto H., Yoshida T., Terada M., Sugimura T. Amplification of the hst-1 gene in human esophageal carcinomas. Jpn J Cancer Res. 1988 May;79(5):584–588. doi: 10.1111/j.1349-7006.1988.tb00026.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tsuda T., Tahara E., Kajiyama G., Sakamoto H., Terada M., Sugimura T. High incidence of coamplification of hst-1 and int-2 genes in human esophageal carcinomas. Cancer Res. 1989 Oct 15;49(20):5505–5508. [PubMed] [Google Scholar]
  22. Varley J. M., Swallow J. E., Brammar W. J., Whittaker J. L., Walker R. A. Alterations to either c-erbB-2(neu) or c-myc proto-oncogenes in breast carcinomas correlate with poor short-term prognosis. Oncogene. 1987;1(4):423–430. [PubMed] [Google Scholar]
  23. Vogelstein B., Fearon E. R., Hamilton S. R., Kern S. E., Preisinger A. C., Leppert M., Nakamura Y., White R., Smits A. M., Bos J. L. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988 Sep 1;319(9):525–532. doi: 10.1056/NEJM198809013190901. [DOI] [PubMed] [Google Scholar]
  24. Wada M., Yokota J., Mizoguchi H., Sugimura T., Terada M. Infrequent loss of chromosomal heterozygosity in human stomach cancer. Cancer Res. 1988 Jun 1;48(11):2988–2992. [PubMed] [Google Scholar]
  25. Wahl G. M. The importance of circular DNA in mammalian gene amplification. Cancer Res. 1989 Mar 15;49(6):1333–1340. [PubMed] [Google Scholar]
  26. Yamamoto T., Ikawa S., Akiyama T., Semba K., Nomura N., Miyajima N., Saito T., Toyoshima K. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature. 1986 Jan 16;319(6050):230–234. doi: 10.1038/319230a0. [DOI] [PubMed] [Google Scholar]
  27. Yasui W., Sumiyoshi H., Hata J., Kameda T., Ochiai A., Ito H., Tahara E. Expression of epidermal growth factor receptor in human gastric and colonic carcinomas. Cancer Res. 1988 Jan 1;48(1):137–141. [PubMed] [Google Scholar]
  28. Yokota J., Wada M., Shimosato Y., Terada M., Sugimura T. Loss of heterozygosity on chromosomes 3, 13, and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9252–9256. doi: 10.1073/pnas.84.24.9252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Yokota J., Wada M., Yoshida T., Noguchi M., Terasaki T., Shimosato Y., Sugimura T., Terada M. Heterogeneity of lung cancer cells with respect to the amplification and rearrangement of myc family oncogenes. Oncogene. 1988 Jun;2(6):607–611. [PubMed] [Google Scholar]
  30. Yokota J., Yamamoto T., Miyajima N., Toyoshima K., Nomura N., Sakamoto H., Yoshida T., Terada M., Sugimura T. Genetic alterations of the c-erbB-2 oncogene occur frequently in tubular adenocarcinoma of the stomach and are often accompanied by amplification of the v-erbA homologue. Oncogene. 1988 Mar;2(3):283–287. [PubMed] [Google Scholar]
  31. Yoshida K., Kyo E., Tsuda T., Tsujino T., Ito M., Niimoto M., Tahara E. EGF and TGF-alpha, the ligands of hyperproduced EGFR in human esophageal carcinoma cells, act as autocrine growth factors. Int J Cancer. 1990 Jan 15;45(1):131–135. doi: 10.1002/ijc.2910450124. [DOI] [PubMed] [Google Scholar]
  32. Yoshida K., Kyo E., Tsujino T., Sano T., Niimoto M., Tahara E. Expression of epidermal growth factor, transforming growth factor-alpha and their receptor genes in human gastric carcinomas; implication for autocrine growth. Jpn J Cancer Res. 1990 Jan;81(1):43–51. doi: 10.1111/j.1349-7006.1990.tb02505.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yoshida K., Tsuda T., Matsumura T., Tsujino T., Hattori T., Ito H., Tahara E. Amplification of epidermal growth factor receptor (EGFR) gene and oncogenes in human gastric carcinomas. Virchows Arch B Cell Pathol Incl Mol Pathol. 1989;57(5):285–290. doi: 10.1007/BF02899093. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES