Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Oct;84(19):6899–6903. doi: 10.1073/pnas.84.19.6899

Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification.

A J Wong 1, S H Bigner 1, D D Bigner 1, K W Kinzler 1, S R Hamilton 1, B Vogelstein 1
PMCID: PMC299192  PMID: 3477813

Abstract

Primary malignant gliomas from 63 patients were analyzed to determine the relationship between amplification of the gene encoding the epidermal growth factor receptor (EGFR) and expression of the corresponding mRNA. Twenty-four tumors were found to have amplified the EGFR gene and amplification of other genes occurred in three additional tumors. Hybridization with synthetic RNA probes was used to quantitate mRNA levels in situ. All 24 tumors with amplification of the EGFR gene had high levels of expression of this gene, while none of the 39 tumors without amplification had increased levels. This shows that, in human gliomas, large increases in the expression of the EGFR gene are invariably associated with alterations in gene structure.

Full text

PDF
6899

Images in this article

Selected References

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

  1. Alitalo K., Schwab M., Lin C. C., Varmus H. E., Bishop J. M. Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1707–1711. doi: 10.1073/pnas.80.6.1707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bigner S. H., Mark J., Bullard D. E., Mahaley M. S., Jr, Bigner D. D. Chromosomal evolution in malignant human gliomas starts with specific and usually numerical deviations. Cancer Genet Cytogenet. 1986 Jun;22(2):121–135. doi: 10.1016/0165-4608(86)90172-x. [DOI] [PubMed] [Google Scholar]
  3. Bigner S. H., Mark J., Mahaley M. S., Bigner D. D. Patterns of the early, gross chromosomal changes in malignant human gliomas. Hereditas. 1984;101(1):103–113. doi: 10.1111/j.1601-5223.1984.tb00455.x. [DOI] [PubMed] [Google Scholar]
  4. Blair D. G., Oskarsson M., Wood T. G., McClements W. L., Fischinger P. J., Vande Woude G. G. Activation of the transforming potential of a normal cell sequence: a molecular model for oncogenesis. Science. 1981 May 22;212(4497):941–943. doi: 10.1126/science.7233190. [DOI] [PubMed] [Google Scholar]
  5. Calabretta B., Kaczmarek L., Ming P. M., Au F., Ming S. C. Expression of c-myc and other cell cycle-dependent genes in human colon neoplasia. Cancer Res. 1985 Dec;45(12 Pt 1):6000–6004. [PubMed] [Google Scholar]
  6. Cox K. H., DeLeon D. V., Angerer L. M., Angerer R. C. Detection of mrnas in sea urchin embryos by in situ hybridization using asymmetric RNA probes. Dev Biol. 1984 Feb;101(2):485–502. doi: 10.1016/0012-1606(84)90162-3. [DOI] [PubMed] [Google Scholar]
  7. Croce C. M. Chromosome translocations and human cancer. Cancer Res. 1986 Dec;46(12 Pt 1):6019–6023. [PubMed] [Google Scholar]
  8. DeFeo D., Gonda M. A., Young H. A., Chang E. H., Lowy D. R., Scolnick E. M., Ellis R. W. Analysis of two divergent rat genomic clones homologous to the transforming gene of Harvey murine sarcoma virus. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3328–3332. doi: 10.1073/pnas.78.6.3328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Downward J., Yarden Y., Mayes E., Scrace G., Totty N., Stockwell P., Ullrich A., Schlessinger J., Waterfield M. D. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature. 1984 Feb 9;307(5951):521–527. doi: 10.1038/307521a0. [DOI] [PubMed] [Google Scholar]
  10. Eissenberg J. C., Cartwright I. L., Thomas G. H., Elgin S. C. Selected topics in chromatin structure. Annu Rev Genet. 1985;19:485–536. doi: 10.1146/annurev.ge.19.120185.002413. [DOI] [PubMed] [Google Scholar]
  11. Erisman M. D., Rothberg P. G., Diehl R. E., Morse C. C., Spandorfer J. M., Astrin S. M. Deregulation of c-myc gene expression in human colon carcinoma is not accompanied by amplification or rearrangement of the gene. Mol Cell Biol. 1985 Aug;5(8):1969–1976. doi: 10.1128/mcb.5.8.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Gonzalez I. L., Gorski J. L., Campen T. J., Dorney D. J., Erickson J. M., Sylvester J. E., Schmickel R. D. Variation among human 28S ribosomal RNA genes. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7666–7670. doi: 10.1073/pnas.82.22.7666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Holliday R. A new theory of carcinogenesis. Br J Cancer. 1979 Oct;40(4):513–522. doi: 10.1038/bjc.1979.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kinzler K. W., Bigner S. H., Bigner D. D., Trent J. M., Law M. L., O'Brien S. J., Wong A. J., Vogelstein B. Identification of an amplified, highly expressed gene in a human glioma. Science. 1987 Apr 3;236(4797):70–73. doi: 10.1126/science.3563490. [DOI] [PubMed] [Google Scholar]
  16. Knudson A. G., Jr Hereditary cancer, oncogenes, and antioncogenes. Cancer Res. 1985 Apr;45(4):1437–1443. [PubMed] [Google Scholar]
  17. 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]
  18. Lee W. H., Murphree A. L., Benedict W. F. Expression and amplification of the N-myc gene in primary retinoblastoma. 1984 May 31-Jun 6Nature. 309(5967):458–460. doi: 10.1038/309458a0. [DOI] [PubMed] [Google Scholar]
  19. Libermann T. A., Nusbaum H. R., Razon N., Kris R., Lax I., Soreq H., Whittle N., Waterfield M. D., Ullrich A., Schlessinger J. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature. 1985 Jan 10;313(5998):144–147. doi: 10.1038/313144a0. [DOI] [PubMed] [Google Scholar]
  20. Lin C. R., Chen W. S., Kruiger W., Stolarsky L. S., Weber W., Evans R. M., Verma I. M., Gill G. N., Rosenfeld M. G. Expression cloning of human EGF receptor complementary DNA: gene amplification and three related messenger RNA products in A431 cells. Science. 1984 May 25;224(4651):843–848. doi: 10.1126/science.6326261. [DOI] [PubMed] [Google Scholar]
  21. Mavilio F., Sposi N. M., Petrini M., Bottero L., Marinucci M., De Rossi G., Amadori S., Mandelli F., Peschle C. Expression of cellular oncogenes in primary cells from human acute leukemias. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4394–4398. doi: 10.1073/pnas.83.12.4394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Merlino G. T., Xu Y. H., Ishii S., Clark A. J., Semba K., Toyoshima K., Yamamoto T., Pastan I. Amplification and enhanced expression of the epidermal growth factor receptor gene in A431 human carcinoma cells. Science. 1984 Apr 27;224(4647):417–419. doi: 10.1126/science.6200934. [DOI] [PubMed] [Google Scholar]
  23. Mintz B., Fleischman R. A. Teratocarcinomas and other neoplasms as developmental defects in gene expression. Adv Cancer Res. 1981;34:211–278. doi: 10.1016/s0065-230x(08)60243-2. [DOI] [PubMed] [Google Scholar]
  24. Nowell P. C. Mechanisms of tumor progression. Cancer Res. 1986 May;46(5):2203–2207. [PubMed] [Google Scholar]
  25. Rothberg P. G., Erisman M. D., Diehl R. E., Rovigatti U. G., Astrin S. M. Structure and expression of the oncogene c-myc in fresh tumor material from patients with hematopoietic malignancies. Mol Cell Biol. 1984 Jun;4(6):1096–1103. doi: 10.1128/mcb.4.6.1096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schimke R. T. Gene amplification in cultured animal cells. Cell. 1984 Jul;37(3):705–713. doi: 10.1016/0092-8674(84)90406-9. [DOI] [PubMed] [Google Scholar]
  27. Schwab M., Alitalo K., Klempnauer K. H., Varmus H. E., Bishop J. M., Gilbert F., Brodeur G., Goldstein M., Trent J. Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature. 1983 Sep 15;305(5931):245–248. doi: 10.1038/305245a0. [DOI] [PubMed] [Google Scholar]
  28. Squire J., Goddard A. D., Canton M., Becker A., Phillips R. A., Gallie B. L. Tumour induction by the retinoblastoma mutation is independent of N-myc expression. Nature. 1986 Aug 7;322(6079):555–557. doi: 10.1038/322555a0. [DOI] [PubMed] [Google Scholar]
  29. Stark G. R., Wahl G. M. Gene amplification. Annu Rev Biochem. 1984;53:447–491. doi: 10.1146/annurev.bi.53.070184.002311. [DOI] [PubMed] [Google Scholar]
  30. Stoscheck C. M., King L. E., Jr Functional and structural characteristics of EGF and its receptor and their relationship to transforming proteins. J Cell Biochem. 1986;31(2):135–152. doi: 10.1002/jcb.240310206. [DOI] [PubMed] [Google Scholar]
  31. Trent J., Meltzer P., Rosenblum M., Harsh G., Kinzler K., Mashal R., Feinberg A., Vogelstein B. Evidence for rearrangement, amplification, and expression of c-myc in a human glioblastoma. Proc Natl Acad Sci U S A. 1986 Jan;83(2):470–473. doi: 10.1073/pnas.83.2.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ullrich A., Coussens L., Hayflick J. S., Dull T. J., Gray A., Tam A. W., Lee J., Yarden Y., Libermann T. A., Schlessinger J. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. 1984 May 31-Jun 6Nature. 309(5967):418–425. doi: 10.1038/309418a0. [DOI] [PubMed] [Google Scholar]
  33. Wong A. J., Ruppert J. M., Eggleston J., Hamilton S. R., Baylin S. B., Vogelstein B. Gene amplification of c-myc and N-myc in small cell carcinoma of the lung. Science. 1986 Jul 25;233(4762):461–464. doi: 10.1126/science.3014659. [DOI] [PubMed] [Google Scholar]
  34. Wyman A. R., White R. A highly polymorphic locus in human DNA. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6754–6758. doi: 10.1073/pnas.77.11.6754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Xu Y. H., Ishii S., Clark A. J., Sullivan M., Wilson R. K., Ma D. P., Roe B. A., Merlino G. T., Pastan I. Human epidermal growth factor receptor cDNA is homologous to a variety of RNAs overproduced in A431 carcinoma cells. 1984 Jun 28-Jul 4Nature. 309(5971):806–810. doi: 10.1038/309806a0. [DOI] [PubMed] [Google Scholar]
  36. Xu Y. H., Richert N., Ito S., Merlino G. T., Pastan I. Characterization of epidermal growth factor receptor gene expression in malignant and normal human cell lines. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7308–7312. doi: 10.1073/pnas.81.23.7308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Yoshimoto K., Hirohashi S., Sekiya T. Increased expression of the c-myc gene without gene amplification in human lung cancer and colon cancer cell lines. Jpn J Cancer Res. 1986 Jun;77(6):540–545. [PubMed] [Google Scholar]
  38. Zimmerman K. A., Yancopoulos G. D., Collum R. G., Smith R. K., Kohl N. E., Denis K. A., Nau M. M., Witte O. N., Toran-Allerand D., Gee C. E. Differential expression of myc family genes during murine development. 1986 Feb 27-Mar 5Nature. 319(6056):780–783. doi: 10.1038/319780a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES