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Medical Oncology

, Volume 15, Issue 4, pp 255–261 | Cite as

Complete sequence of p53 gene in 20 patients with lung cancer: comparison with chemosensitivity and immunohistochemistry

  • Daniel Brattström
  • Michael Bergqvist
  • Kristina Lamberg
  • Wolfgang Kraaz
  • Lena Scheibenflug
  • Gunnar Gustafsson
  • Mats Inganas
  • Gunnar Wagenius
  • Ola Brodin
Paper

Abstract

In this study the entirep53 complementary DNA has been sequenced in 20 non-small cell lung carcinomas (NSCLC) and the results correlated with chemosensitivity, immunohistochemistry and clinical data. Ten patients had mutations inp53, 8 missense mutations and 2 nonsense mutations. The method discovered two mutations never described previously and two other mutations that have never been described before in connection with NSCLC tumours. Chemosensitivity data, according to a short-term assay (FMCA), indicated that tumours with p53 mutation were more resistant to cisplatin and cyclophosphamide. Immunohistochemical studied demonstrated a 70% concordance between over-expression of p53 protein and mutation inp53. No conclusions or trends could be drawn from the immunohistochemical studies ofBcl-2 andBax.

Keywords

p53 Bax Bcl-2 immunohistochemistry drug resistance mutation cDNA sequencing ALFexpress non-small cell lung cancer NSCLC 

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References

  1. 1.
    Levine AJ, Momand J, Finlay CA. The p53 tumour suppressor gene.Nature 1991;351: 453–456.PubMedCrossRefGoogle Scholar
  2. 2.
    Takahashi Tet al. p53: a frequent target for genetic abnormalities in lung cancer.Science 1989;246: 491–494.PubMedCrossRefGoogle Scholar
  3. 3.
    Cho Y, Gorina S, Jeffrey PD, Pavletich NP. Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations [see comments].Science 1994;265: 346–355.PubMedCrossRefGoogle Scholar
  4. 4.
    Ory K, Legros Y, Auguin C, Soussi T. Analysis of the most representative tumour-derived p53 mutants reveals that changes in protein conformation are not correlated with loss of transactivation or inhibition of cell proliferation.EMBO J 1994;13: 3496–3504.PubMedGoogle Scholar
  5. 5.
    Williams Cet al. Assessment of sequence-based p53 gene analysis in human breast cancer: messenger RNA in comparison with genomic DNA targets.Clin Chem 1998;44: 455–462.PubMedGoogle Scholar
  6. 6.
    Kawasaki Met al. p53 immunostaining predicts chemiosensitivity in non-small cell lung cancer: a preliminary report.Cancer J Sci Am 1996;2: 217.PubMedGoogle Scholar
  7. 7.
    Rusch Vet al.: Aberrant p53 expression predicts clinical resistance to cisplatin-based chemotherapy in locally advanced non-small cell lung cancer.Cancer Res 1995;55: 5038–5042.PubMedGoogle Scholar
  8. 8.
    Fujiwara Tet al. Induction of chemosensitivity in human lung cancer cellsin vivo by adenovirus-mediated transfer of the wild-type p53 gene.Cancer Res 1994;54: 2287–2291.PubMedGoogle Scholar
  9. 9.
    Elledge RM. Assessing p53 status in breast cancer prognosis: where should you put the thermometer if you think your p53 is sick? [editorial].J Natl Cancer Inst 1996;88: 141–143.PubMedCrossRefGoogle Scholar
  10. 10.
    Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 hetero-dimerizesin vivo with a conserved homolog, Bax, that accelerates programmed cell death.Cell 1993;74: 609–619.PubMedCrossRefGoogle Scholar
  11. 11.
    White E. Life, death, and the pursuit of apoptosis.Genes Dev 1996;10: 1–15.PubMedCrossRefGoogle Scholar
  12. 12.
    Gascoyne RD, Krajewska M, Krajewski S, Connors JM, Reed JC. Prognostic significance of Bax protein expression in diffuse aggressive non-Hodgkin's lymphoma.Blood 1997;90: 3173–3178.PubMedGoogle Scholar
  13. 13.
    Marx Det al. Differential expression of apoptosis associated genes bax and bcl-2 in ovarian cancer.Anticancer Res 1997;17: 2233–2240.PubMedGoogle Scholar
  14. 14.
    Apolinario RMet al. Prognostic value of the expression of p53, bcl-2, and bax oncoproteins, and neovascularization in patients with radically resected non-small cell lung cancer.J Clin Oncol 1997;15: 2456–2466.PubMedGoogle Scholar
  15. 15.
    Sjogren Set al. The p53 gene in breast cancer: prognostic value of complementary DNA sequencing versus immunohistochemistry.J Natl Cancer Inst 1996;88: 173–182.PubMedCrossRefGoogle Scholar
  16. 16.
    Larsson R, Nygren P. Pharmacological modification of multi-drug resistance (MDR)in vitro detected by a novel fluorometric microculture cytotoxicity assay. Reversal of resistance and selective cytotoxic actions of cyclosporin A and verapamil on MDR leukemia T-cells.Int J Cancer 1990;46: 67–72.PubMedCrossRefGoogle Scholar
  17. 17.
    Nygren Pet al. Feasibility of the fluorometric microculture cytotoxicity assay (FMCA) for cytotoxic drug sensitivity testing of tumor cells from patients with acute lymphoblastic leukemia.Leukemia 1992;6: 1121–1128.PubMedGoogle Scholar
  18. 18.
    Cattoretti Get al. Antigen unmasking on formalin-fixed, paraffin-embedded tissue sections [see comments].J Pathol 1993;171: 83–98.PubMedCrossRefGoogle Scholar
  19. 19.
    Vojtesek B, Bartek J, Midgley CA, Lane DP. An immunochemical analysis of the human nuclear phosphoprotein p53. New monoclonal antibodies and epitope mapping using recombinant p53.J Immunol Methods 1992;151: 237–244.PubMedCrossRefGoogle Scholar
  20. 20.
    Cariello NF, Beroud C, Soussi T. Database and software for the analysis of mutations at the human p53 gene.Nucleic Acids Res 1994;22: 3549–3550.PubMedGoogle Scholar
  21. 21.
    Jansson Tet al. p53 status predicts survival in breast cancer patients treated with or without postoperative radiotherapy: a novel hypothesis based on clinical findings.J Clin Oncol 1995;13: 2745–2751.PubMedGoogle Scholar
  22. 22.
    Bergh J, Norberg T, Sjogren S, Lindgren A, Holmberg L. Complete sequencing of the p53 gene provides prognostic information in breast cancer patients, particularly in relation to adjuvant systemic therapy and radiotherapy.Nat Med 1995;1: 1029–1034.PubMedCrossRefGoogle Scholar
  23. 23.
    Kressner U. Prognostic markers in colorectal cancer: aspects of proliferation, tumour stroma and genetic changes [Dissertation from the Faculty of Medicine 718.]. Uppsala University: Uppsala, 1997, 60 p.Google Scholar
  24. 24.
    Winter SFet al. Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutation.Cancer Res 1992;52: 4168–4174.PubMedGoogle Scholar
  25. 25.
    Bergqvist Met al. p53 auto-antibodies in non-small cell lung cancer patients, can predict increased life expectancy after radiotherapy.Anticancer Res 1998;18: 1999–2002.PubMedGoogle Scholar
  26. 26.
    Lee JSet al. Expression of p53 oncoprotein in non-small-cell lung cancer: a favorable prognostic factor.J Clin Oncol 1995;13: 1893–1903.PubMedGoogle Scholar
  27. 27.
    Prives C. How loops, beta sheets, and alpha helices help us to understand p53.Cell 1994;78: 543–546.PubMedCrossRefGoogle Scholar
  28. 28.
    Lin J, Chen J, Elenbaas B, Levine AJ. Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein.Genes Dev 1994;8: 1235–1246.PubMedCrossRefGoogle Scholar
  29. 29.
    Egle Aet al. Expression of Apo-1/Fas (CD95), Bcl-2, Bax and Bcl-x in myeloma cell lines: relationship between responsiveness to anti-Fas mab and p53 functional status.Br J Haematol 1997;97: 418–428.PubMedCrossRefGoogle Scholar

Copyright information

© Stockton Press 1998

Authors and Affiliations

  • Daniel Brattström
    • 1
  • Michael Bergqvist
    • 1
  • Kristina Lamberg
    • 2
  • Wolfgang Kraaz
    • 3
  • Lena Scheibenflug
    • 3
  • Gunnar Gustafsson
    • 4
  • Mats Inganas
    • 5
  • Gunnar Wagenius
    • 1
  • Ola Brodin
    • 1
  1. 1.Department of Oncology, Uppsala Akademiska HospitalUppsala UniversityUppsalaSweden
  2. 2.Department of Pulmonary Medicine, Uppsala Akademiska HospitalUppsala UniversityUppsalaSweden
  3. 3.Department of Pathology, Uppsala Akademiska HospitalUppsala UniversityUppsalaSweden
  4. 4.Department of Thoracic Surgery, Uppsala Akademiska HospitalUppsala UniversityUppsalaSweden
  5. 5.Department of Pharmacia BiotechUppsalaSweden

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