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:

High-resolution single-nucleotide polymorphism array and clustering analysis of loss of heterozygosity in human lung cancer cell lines

Oncogene volume 23, pages 2716–2726 (2004)Cite this article

Abstract

Chromosomal loss of heterozygosity (LOH) is a common mechanism for the inactivation of tumor suppressor genes in human epithelial cancers. Hybridization to single-nucleotide polymorphism (SNP) arrays is an efficient method to detect genome-wide cancer LOH. Here, we survey LOH patterns in a panel of 33 human lung cancer cell lines using SNP array hybridization containing 1500 SNPs. We compared the LOH patterns generated by SNP array hybridization to those previously obtained by 399 microsatellite markers and find a high degree of concordance between the two methods. A novel informatics platform, dChipSNP, was used to perform hierarchical tumor clustering based on genome-wide LOH patterns. We demonstrate that this method can separate non-small-cell and small-cell lung cancer samples based on their shared LOH. Furthermore, we analysed seven human lung cancer cell lines using a novel 10 000 SNP array and demonstrate that this is an efficient and reliable method of high-density allelotyping. Using this array, we identified small regions of LOH that were not detected by lower density SNP arrays or by standard microsatellite marker panels.

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
Figure 3
Figure 4

Similar content being viewed by others

References

  • Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson Jr J, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO and Staudt LM . (2000). Nature, 403, 503–511.

  • Beer DG, Kardia SL, Huang CC, Giordano TJ, Levin AM, Misek DE, Lin L, Chen G, Gharib TG, Thomas DG, Lizyness ML, Kuick R, Hayasaka S, Taylor JM, Iannettoni MD, Orringer MB and Hanash S . (2002). Nat. Med., 8, 816–824.

  • Bhattacharjee A, Richards WG, Staunton J, Li C, Monti S, Vasa P, Ladd C, Beheshti J, Bueno R, Gillette M, Loda M, Weber G, Mark EJ, Lander ES, Wong W, Johnson BE, Golub TR, Sugarbaker DJ and Meyerson M . (2001). Proc. Natl. Acad. Sci. USA, 98, 13790–13795.

  • Dumur CI, Dechsukhum C, Ware JL, Cofield SS, Best AM, Wilkinson DS, Garrett CT and Ferreira-Gonzalez A . (2003). Genomics, 81, 260–269.

  • Eisen MB, Spellman PT, Brown PO and Botstein D . (1998). Proc. Natl. Acad. Sci. USA, 95, 14863–14868.

  • Fong KM, Zimmerman PV and Smith PJ . (1994). Genes Chromosomes Cancer, 10, 183–189.

  • Fong KM, Zimmerman PV and Smith PJ . (1995). Cancer Res., 55, 220–223.

  • Garber ME, Troyanskaya OG, Schluens K, Petersen S, Thaesler Z, Pacyna-Gengelbach M, van de Rijn M, Rosen GD, Perou CM, Whyte RI, Altman RB, Brown PO, Botstein D and Petersen I . (2001). Proc. Natl. Acad. Sci. USA, 98, 13784–13789.

  • Girard L, Zochbauer-Muller S, Virmani AK, Gazdar AF and Minna JD . (2000). Cancer Res., 60, 4894–4906.

  • Golub TR, Slonim DK, Tamayo P, Huard C, Gaasenbeek M, Mesirov JP, Coller H, Loh ML, Downing JR, Caligiuri MA, Bloomfield CD and Lander ES . (1999). Science, 286, 531–537.

  • Hoque MO, Lee CC, Cairns P, Schoenberg M and Sidransky D . (2003). Cancer Res., 63, 2216–2222.

  • Janne PA, Tanenbaum DM, Beheshti J, Mark EJ, Johnson BE and Meyerson ML . (2002). Proc. Am. Assoc. Can. Res., 43, 3147a.

  • Jemal A, Murray T, Samuels A, Ghafoor A, Ward E and Thun MJ . (2003). CA Cancer J. Clin., 53, 5–26.

  • Kennedy GC, Matsuzaki H, Dong S, Liu WM, Huang J, Liu G, Su X, Cao M, Chen W, Zhang J, Liu W, Yang G, Di X, Ryder T, He Z, Surti U, Phillips MS, Boyce-Jacino MT, Fodor SP and Jones KW . (2003). Nat. Biotechnol., 21, 1233–1237.

  • Li C and Wong WH . (2001). Proc. Natl. Acad. Sci. USA, 98, 31–36.

  • Lieberfarb ME, Lin M, Lechpammer M, Li C, Tanenbaum DM, Febbo PG, Wright RL, Shim J, Kantoff PW, Loda M, Meyerson M and Sellers WR . (2003). Cancer Res., 63, 4781–4785.

  • Lin M, Wei L-J, Sellers WR, Lieberfarb M, Wong WH and Li C . (2003). Bioinformatics, (in press).

  • Lindblad-Toh K, Tanenbaum DM, Daly MJ, Winchester E, Lui WO, Villapakkam A, Stanton SE, Larsson C, Hudson TJ, Johnson BE, Lander ES and Meyerson M . (2000). Nat. Biotechnol., 18, 1001–1005.

  • Mei R, Galipeau PC, Prass C, Berno A, Ghandour G, Patil N, Wolff RK, Chee MS, Reid BJ and Lockhart DJ . (2000). Genome Res., 10, 1126–1137.

  • Mitsudomi T, Oyama T, Nishida K, Ogami A, Osaki T, Sugio K, Yasumoto K, Sugimachi K and Gazdar AF . (1996). Clin. Cancer Res., 2, 1185–1189.

  • Osada H and Takahashi T . (2002). Oncogene, 21, 7421–7434.

  • Primdahl H, Wikman FP, von der Maase H, Zhou XG, Wolf H and Orntoft TF . (2002). J. Natl. Cancer Inst., 94, 216–223.

  • Reich DE, Gabriel SB and Altshuler D . (2003). Nat. Genet., 33, 457–458.

  • Sachidanandam R, Weissman D, Schmidt SC, Kakol JM, Stein LD, Marth G, Sherry S, Mullikin JC, Mortimore BJ, Willey DL, Hunt SE, Cole CG, Coggill PC, Rice CM, Ning Z, Rogers J, Bentley DR, Kwok PY, Mardis ER, Yeh RT, Schultz B, Cook L, Davenport R, Dante M, Fulton L, Hillier L, Waterston RH, McPherson JD, Gilman B, Schaffner S, Van Etten WJ, Reich D, Higgins J, Daly MJ, Blumenstiel B, Baldwin J, Stange-Thomann N, Zody MC, Linton L, Lander ES and Altshuler D . (2001). Nature, 409, 928–933.

  • Sekido Y, Fong KM and Minna JD . (2003). Annu. Rev. Med., 54, 73–87.

  • Stanton SE, Shin SW, Johnson BE and Meyerson M . (2000). Genes Chromosomes Cancer, 27, 323–331.

  • Tseng JE, Kemp BL, Khuri FR, Kurie JM, Lee JS, Zhou X, Liu D, Hong WK and Mao L . (1999). Cancer Res., 59, 4798–4803.

  • Virmani AK, Fong KM, Kodagoda D, McIntire D, Hung J, Tonk V, Minna JD and Gazdar AF . (1998). Genes Chromosomes Cancer, 21, 308–319.

  • Wang ZC, Lin M, Wei L-J, Li C, Miron A, Lodeiro G, Harris L, Ramaswamy S, Tanenbaum DM, Meyerson M, Iglehart JD and Richardson A . (2003). Cancer Res., (in press).

  • Zabarovsky ER, Lerman MI and Minna JD . (2002). Oncogene, 21, 6915–6935.

Download references

Acknowledgements

This work is supported by grants from the National Cancer Institute R01CA92824 (DC), the National Institutes of Health 2P30 CA06516-39 (CL) and 1K12CA87723-01 (PAJ), the American Cancer Society RSG-03-240-01-MGO (MM), the Pew Scholars in the Biomedical Sciences (MM), the Flight Attendant Medical Research Institute (MM), the Dunkin Donuts Rising Star Award (PAJ), The Arthur and Rochelle Belfer Foundation (CL and MM), Lung Cancer SPORE P50CA70907 (JM) and The Longenbaugh Foundation (JM).

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA

    Pasi A Jänne, Xiaojun Zhao, Tzu-Hsiu Chen, Bruce E Johnson & Matthew Meyerson

  2. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

    Pasi A Jänne & Bruce E Johnson

  3. Department of Biostatistical Sciences, Dana Farber Cancer Institute, Boston, MA, USA

    Cheng Li

  4. Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA

    Cheng Li

  5. Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Luc Girard & John Minna

  6. Departments of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Luc Girard & John Minna

  7. Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA

    David C Christiani

  8. Department of Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    David C Christiani

Authors
  1. Pasi A Jänne
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cheng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaojun Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luc Girard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tzu-Hsiu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. John Minna
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. David C Christiani
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bruce E Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Matthew Meyerson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matthew Meyerson.

Additional information

Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc) and also at research.dfci.harvard.edu/meyersonlab/snp/janne-oncogene2004

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jänne, P., Li, C., Zhao, X. et al. High-resolution single-nucleotide polymorphism array and clustering analysis of loss of heterozygosity in human lung cancer cell lines. Oncogene 23, 2716–2726 (2004). https://doi.org/10.1038/sj.onc.1207329

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207329

Keywords

This article is cited by

Search

Advanced search

Quick links