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.

  • Original Paper
  • Published:

Adenomatous polyposis coli gene promoter hypermethylation in non-small cell lung cancer is associated with survival

Oncogene volume 20, pages 3528–3532 (2001)Cite this article

Abstract

Methylation of 5′ CpG islands in promoter and upstream coding regions has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. The purpose of this study was to determine whether hypermethylation of the adenomatous polyposis coli (APC) gene promoter occurs in primary non-small cell lung cancer (NSCLC), and whether hypermethylated APC has any relationship with survival. APC promoter 1A methylation was determined in normal and corresponding tumor tissue from 91 NSCLC patients and in a control group of 10 patients without cancer, using a quantitative fluorogenic real-time PCR (Taqman®) system. APC promoter methylation was detectable in 86 (95%) of 91 tumor samples, but also in 80 (88%) of 91 normal samples of NSCLC patients, and in only two (20%) of 10 normal lung tissues of the control group. The median level of APC promoter methylation was 4.75 in tumor compared to 1.57 in normal lung tissue (P<0.001). Patients with low methylation status showed significantly longer survival than did patients with high methylation status (P=0.041). In a multivariate analysis of prognostic factors, APC methylation was a significant independent prognostic factor (P=0.044), as were pT (P=0.050) and pN (P<0.001) classifications. This investigation shows that APC gene promoter methylation occurs in the majority of primary NSCLCs. High APC promoter methylation is significantly associated with inferior survival, showing promise as a biomarker of biologically aggressive disease in NSCLC.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2

Similar content being viewed by others

References

  • Baylin SB, Herman JG, Graff JR, Vertino PM, Issa JP . 1998 Adv. Cancer Res. 72: 141–196

  • Eads CA, Danenberg KD, Kawakami K, Saltz LB, Danenberg PV, Laird PW . 1999 Cancer Res. 59: 2302–2306

  • Eads CA, Danenberg KD, Kawakami K, Saltz LB, Blake C, Shibata D, Danenberg PV, Laird PW . 2000 Nucleic. Acids. Res. 28: E32

  • Eguichi K, Kanai K, Hirohasi S . 1997 Cancer Res. 57: 4913–4915

  • Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB, Herman JG . 1999 Cancer Res. 59: 67–70

  • Esteller M, Sparks A, Toyota M, Sanchez-Cespedes M, Capalla G, Peinando MA, Gonzalez S, Tarafa G, Sidransky D, Meltzer SJ, Baylin SB, Herman JG . 2000 Cancer Res. 60: 4366–4371

  • Ginsberg RJ, Vokes EE, Raben A . 1997 Cancer: Principles in Practice of Oncology Philadelphia: Lippincott-Raven Publishers pp. 858–910

    Google Scholar 

  • Halpern J . 1982 Biometrics 38: 1017–1023

  • Heid CA, Stevens J, Livak KJ, Williams PM . 1996 Genome Res. 6: 986–994

  • Hiltunen MO, Alhonen L, Koistinaho J, Myohanen S, Paakkonen M, Marin S, Kosma VM, Janne J . 1997 Int. J. Cancer 70: 644–648

  • Jones PA, Laird PW . 1999 Nat. Genet. 2: 163–167

  • Kawakami K, Brabender J, Lord RV, Groshen S, Greenwald BD, Krasna MJ, Jing Y, Fleisher SA, Abraham JM, Beer DG, Sidransky D, Huss HT, DeMeester TR, Eads C, Laird PW, Ilsen DH, Kelsen DP, Harpole D, Moore MB, Danenberg KD, Danenberg PV, Meltzer SJ . 2000 J. Natl. Cancer Inst. 92: 1805–1811

  • Landis SH, Murray T, Bolden A, Wingo PA . 1998 CA Cancer J. Clin. 48: 6–29

  • Merlo A, Herman JG, Mo L, Lee DJ, Gabrielson E, Burger PC, Baylin SB, Sidransky D . 1995 Nat. Med. 7: 686–692

  • Miller R, Siegmund D . 1982 Biometrics 38: 1011–1016

  • Olek A, Oswald J, Walter JA . 1996 Nucleic. Acids. Res. 24: 5064–5066

  • Pike MC . 1972 J. R. Stat. Soc. Series A. 135: 210–213

  • Tang X, Khuri FR, Lee JJ, Kemp BL, Liu D, Hong WK, Mao L . 2000 J. Natl. Cancer Inst. 92: 1511–1516

  • Tsuchiya T, Tamura G, Satoh K, Endoh Y, Sakata K, Jin Z, Motoyama T, Usuba O, Kimura W, Nishizuka S, Wilson KT, James SP, Fleisher AS, Zou T, Silverberg SG, Kong D, Meltzer SJ . 2000 Oncogene 32: 3642–3646

Download references

Acknowledgements

Supported by Hubert Burda Foundation for Cancer Research, Germany (to J Brabender), NCI grant RO1 CA71716 (to PV Danenberg), NCI grants CA85069, CA78843, CA77057, DK47717, and DK53620 (to SJ Meltzer); and by the Medical Research Service, Department of Veterans Affairs (to SJ Meltzer).

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, 90033, California, CA, USA

    Jan Brabender, Kathleen D Danenberg, JiMin Park, Dennis Salonga, Jonathan Singer & Peter V Danenberg

  2. Department of Surgery, University of Southern California, Los Angeles, 90033, California, CA, USA

    Reginald V Lord

  3. Department of Pathology, University of Southern California, Los Angeles, 90033, California, CA, USA

    Kumari Wickramasinghe & Christopher E Lum

  4. Department of Visceral and Vascular Surgery, University of Cologne, Cologne, 50931, Germany

    Jan Brabender, Ralf Metzger, Paul M Schneider & Arnulf H Hölscher

  5. Division of Head and Neck Cancer Research, Johns Hopkins University, Baltimore, 21231, Maryland, MD, USA

    Henning Usadel & David Sidransky

  6. Department of Medicine, Greenebaum Cancer Center, University of Maryland School of Medicine and Baltimore VA Hospital, Baltimore, 21201, Maryland MD, USA

    Stephen J Meltzer

Authors
  1. Jan Brabender
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Henning Usadel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kathleen D Danenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ralf Metzger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paul M Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Reginald V Lord
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kumari Wickramasinghe
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Christopher E Lum
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. JiMin Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Dennis Salonga
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jonathan Singer
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. David Sidransky
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Arnulf H Hölscher
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Stephen J Meltzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Peter V Danenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brabender, J., Usadel, H., Danenberg, K. et al. Adenomatous polyposis coli gene promoter hypermethylation in non-small cell lung cancer is associated with survival. Oncogene 20, 3528–3532 (2001). https://doi.org/10.1038/sj.onc.1204455

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204455

Keywords

Search

Advanced search

Quick links