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. 1987 Jun;79(6):1629–1634. doi: 10.1172/JCI112999

myc family oncogene amplification in tumor cell lines established from small cell lung cancer patients and its relationship to clinical status and course.

B E Johnson, D C Ihde, R W Makuch, A F Gazdar, D N Carney, H Oie, E Russell, M M Nau, J D Minna
PMCID: PMC424486  PMID: 3034978

Abstract

44 small cell lung cancer cell lines established from 227 patients were studied for myc family DNA amplification (c-myc, N-myc, and L-myc). Two of 19 lines (11%) established from untreated patients' tumors had DNA amplification (one N-myc and one L-myc), compared with 11 of 25 (5 c-myc, 3 N-myc, and 3 L-myc) cell lines (44%) established from relapsed patients' tumors (P = 0.04). The 19 patients who had tumor cell lines established before chemotherapy treatment survived a median of 14 wk compared with 48 wk for the 123 extensive stage patients who did not have cell lines established (P less than 0.001). Relapsed patients whose cell lines had c-myc DNA amplification survived a shorter period (median of 33 wk) than patients whose cell lines did not have c-myc amplification (median of 53 wk; P = 0.04). We conclude that myc family DNA amplification is more common in tumor cell lines established from treated than untreated patients' tumors, and c-myc amplification in treated patients' tumor cell lines is associated with shortened survival.

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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. Battey J., Moulding C., Taub R., Murphy W., Stewart T., Potter H., Lenoir G., Leder P. The human c-myc oncogene: structural consequences of translocation into the IgH locus in Burkitt lymphoma. Cell. 1983 Oct;34(3):779–787. doi: 10.1016/0092-8674(83)90534-2. [DOI] [PubMed] [Google Scholar]
  3. Brodeur G. M., Seeger R. C., Schwab M., Varmus H. E., Bishop J. M. Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science. 1984 Jun 8;224(4653):1121–1124. doi: 10.1126/science.6719137. [DOI] [PubMed] [Google Scholar]
  4. Carney D. N., Gazdar A. F., Bepler G., Guccion J. G., Marangos P. J., Moody T. W., Zweig M. H., Minna J. D. Establishment and identification of small cell lung cancer cell lines having classic and variant features. Cancer Res. 1985 Jun;45(6):2913–2923. [PubMed] [Google Scholar]
  5. Cohen M. H., Ihde D. C., Bunn P. A., Jr, Fossieck B. E., Jr, Matthews M. J., Shackney S. E., Johnston-Early A., Makuch R., Minna J. D. Cyclic alternating combination chemotherapy for small cell bronchogenic carcinoma. Cancer Treat Rep. 1979 Feb;63(2):163–170. [PubMed] [Google Scholar]
  6. Collins S., Groudine M. Amplification of endogenous myc-related DNA sequences in a human myeloid leukaemia cell line. Nature. 1982 Aug 12;298(5875):679–681. doi: 10.1038/298679a0. [DOI] [PubMed] [Google Scholar]
  7. GEHAN E. A. A GENERALIZED WILCOXON TEST FOR COMPARING ARBITRARILY SINGLY-CENSORED SAMPLES. Biometrika. 1965 Jun;52:203–223. [PubMed] [Google Scholar]
  8. Gazdar A. F., Carney D. N., Nau M. M., Minna J. D. Characterization of variant subclasses of cell lines derived from small cell lung cancer having distinctive biochemical, morphological, and growth properties. Cancer Res. 1985 Jun;45(6):2924–2930. [PubMed] [Google Scholar]
  9. Hieter P. A., Hollis G. F., Korsmeyer S. J., Waldmann T. A., Leder P. Clustered arrangement of immunoglobulin lambda constant region genes in man. Nature. 1981 Dec 10;294(5841):536–540. doi: 10.1038/294536a0. [DOI] [PubMed] [Google Scholar]
  10. Ihde D. C., Makuch R. W., Carney D. N., Bunn P. A., Cohen M. H., Matthews M. J., Minna J. D. Prognostic implications of stage of disease and sites of metastases in patients with small cell carcinoma of the lung treated with intensive combination chemotherapy. Am Rev Respir Dis. 1981 May;123(5):500–507. doi: 10.1164/arrd.1981.123.5.500. [DOI] [PubMed] [Google Scholar]
  11. Johnson B. E., Battey J., Linnoila I., Becker K. L., Makuch R. W., Snider R. H., Carney D. N., Minna J. D. Changes in the phenotype of human small cell lung cancer cell lines after transfection and expression of the c-myc proto-oncogene. J Clin Invest. 1986 Aug;78(2):525–532. doi: 10.1172/JCI112604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Johnson B. E., Ihde D. C., Bunn P. A., Becker B., Walsh T., Weinstein Z. R., Matthews M. J., Whang-Peng J., Makuch R. W., Johnston-Early A. Patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation. Data on potential cures, chronic toxicities, and late relapses after a five- to eleven-year follow-up. Ann Intern Med. 1985 Sep;103(3):430–438. doi: 10.7326/0003-4819-103-3-430. [DOI] [PubMed] [Google Scholar]
  13. Kohl N. E., Kanda N., Schreck R. R., Bruns G., Latt S. A., Gilbert F., Alt F. W. Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell. 1983 Dec;35(2 Pt 1):359–367. doi: 10.1016/0092-8674(83)90169-1. [DOI] [PubMed] [Google Scholar]
  14. Kozbor D., Croce C. M. Amplification of the c-myc oncogene in one of five human breast carcinoma cell lines. Cancer Res. 1984 Feb;44(2):438–441. [PubMed] [Google Scholar]
  15. 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]
  16. Little C. D., Nau M. M., Carney D. N., Gazdar A. F., Minna J. D. Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature. 1983 Nov 10;306(5939):194–196. doi: 10.1038/306194a0. [DOI] [PubMed] [Google Scholar]
  17. Livingston R. B., Moore T. N., Heilbrun L., Bottomley R., Lehane D., Rivkin S. E., Thigpen T. Small-cell carcinoma of the lung: combined chemotherapy and radiation: a Southwest Oncology Group study. Ann Intern Med. 1978 Feb;88(2):194–199. doi: 10.7326/0003-4819-88-2-194. [DOI] [PubMed] [Google Scholar]
  18. Morstyn G., Ihde D. C., Lichter A. S., Bunn P. A., Carney D. N., Glatstein E., Minna J. D. Small cell lung cancer 1973-1983: early progress and recent obstacles. Int J Radiat Oncol Biol Phys. 1984 Apr;10(4):515–539. doi: 10.1016/0360-3016(84)90032-4. [DOI] [PubMed] [Google Scholar]
  19. Nakasato F., Sakamoto H., Mori M., Hayashi K., Shimosato Y., Nishi M., Takao S., Nakatani K., Terada M., Sugimura T. Amplification of the c-myc oncogene in human stomach cancers. Gan. 1984 Sep;75(9):737–742. [PubMed] [Google Scholar]
  20. Nau M. M., Brooks B. J., Battey J., Sausville E., Gazdar A. F., Kirsch I. R., McBride O. W., Bertness V., Hollis G. F., Minna J. D. L-myc, a new myc-related gene amplified and expressed in human small cell lung cancer. Nature. 1985 Nov 7;318(6041):69–73. doi: 10.1038/318069a0. [DOI] [PubMed] [Google Scholar]
  21. Nau M. M., Brooks B. J., Jr, Carney D. N., Gazdar A. F., Battey J. F., Sausville E. A., Minna J. D. Human small-cell lung cancers show amplification and expression of the N-myc gene. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1092–1096. doi: 10.1073/pnas.83.4.1092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Reynolds C. P., Frenkel E. P., Smith R. G. Growth characteristics of neuroblastoma in vitro correlate with patient survival. Trans Assoc Am Physicians. 1980;93:203–211. [PubMed] [Google Scholar]
  23. Saksela K., Bergh J., Lehto V. P., Nilsson K., Alitalo K. Amplification of the c-myc oncogene in a subpopulation of human small cell lung cancer. Cancer Res. 1985 Apr;45(4):1823–1827. [PubMed] [Google Scholar]
  24. Sausville E., Carney D., Battey J. The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line. J Biol Chem. 1985 Aug 25;260(18):10236–10241. [PubMed] [Google Scholar]
  25. 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]
  26. Seeger R. C., Brodeur G. M., Sather H., Dalton A., Siegel S. E., Wong K. Y., Hammond D. Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med. 1985 Oct 31;313(18):1111–1116. doi: 10.1056/NEJM198510313131802. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. 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]
  29. Whang-Peng J., Bunn P. A., Jr, Kao-Shan C. S., Lee E. C., Carney D. N., Gazdar A., Minna J. D. A nonrandom chromosomal abnormality, del 3p(14-23), in human small cell lung cancer (SCLC). Cancer Genet Cytogenet. 1982 Jun;6(2):119–134. doi: 10.1016/0165-4608(82)90077-2. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Yokota J., Tsunetsugu-Yokota Y., Battifora H., Le Fevre C., Cline M. J. Alterations of myc, myb, and rasHa proto-oncogenes in cancers are frequent and show clinical correlation. Science. 1986 Jan 17;231(4735):261–265. doi: 10.1126/science.3941898. [DOI] [PubMed] [Google Scholar]

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