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  • Oncogenomics
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Genome-wide DNA copy number alterations in head and neck squamous cell carcinomas with or without oncogene-expressing human papillomavirus

Oncogene volume 25, pages 2558–2564 (2006)Cite this article

Abstract

Oncogene-expressing human papillomavirus type 16 (HPV16) is found in a subset of head and neck squamous cell carcinomas (HNSCC). HPV16 drives carcinogenesis by inactivating p53 and pRb with the viral oncoproteins E6 and E7, paralleled by a low level of mutations in TP53 and allelic loss at 3p, 9p, and 17p, genetic changes frequently found in HNSCCs of nonviral etiology. We hypothesize that two pathways to HNSCC exist: one determined by HPV16 and the other by environmental carcinogens. To define the critical genetic events in these two pathways, we now present a detailed genome analysis of HNSCC with and without HPV16 involvement by employing high-resolution microarray comparative genomic hybridization. Four regions showed alterations in HPV-negative tumors that were absent in HPV-positive tumors: losses at 3p11.2–26.3, 5q11.2–35.2, and 9p21.1–24, and gains/amplifications at 11q12.1–13.4. Also, HPV16-negative tumors demonstrated loss at 18q12.1–23, in contrast to gain in HPV16-positive tumors. Seven regions were altered at high frequency (>33%) in both groups: gains at 3q22.2-qter, 5p15.2-pter, 8p11.2-qter, 9q22–34.1, and 20p–20q, and losses at 11q14.1-qter and 13q11–33. These data show that HNSCC arising by environmental carcinogens are characterized by genetic alterations that differ from those observed in HPV16-induced HNSCC, and most likely occur early in carcinogenesis. A number of genetic changes are shared in both tumor groups and can be considered crucial in the later stages of HNSCC progression.

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References

  • Ahomadegbe JC, Barrois M, Fogel S, Le Bihan ML, Douc-Rasy S, Duvillard P et al. (1995). Oncogene 10: 1217–1227.

  • Beder LB, Gunduz M, Ouchida M, Fukushima K, Gunduz E, Ito S et al. (2003). Lab Invest 83: 99–105.

  • Bockmuhl U, Schluns K, Kuchler I, Petersen S, Petersen I . (2000). Am J Pathol 157: 369–375.

  • Braakhuis BJM, Leemans CR, Brakenhoff RH . (2004a). J Oral Pathol Med 33: 317–322.

  • Braakhuis BJM, Snijders PJF, Keune WJH, Meijer CJLM, Ruijter-Schippers HJ, Leemans CR et al. (2004b). J Natl Cancer Inst 96: 998–1006.

  • Califano J, van der Riet P, Westra W, Nawroz H, Clayman G, Piantadosi S et al. (1996). Cancer Res 56: 2488–2492.

  • Dahlgren L, Mellin H, Wangsa D, Heselmeyer-Haddad K, Bjornestal L, Lindholm J et al. (2003). Int J Cancer 107: 244–249.

  • Erber R, Conradt C, Homann N, Enders C, Finckh M, Dietz A et al. (1998). Oncogene 16: 1671–1679.

  • Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L et al. (2000). J Natl Cancer Inst 92: 709–720.

  • Gollin SM . (2001). Head Neck 23: 238–253.

  • Hahn SA, Schutte M, Hoque ATMS, Moskaluk CA, Dacosta LT, Rozenblum E et al. (1996). Science 271: 350–353.

  • Herrero R, Castellsague X, Pawlita M, Lissowska J, Kee F, Balaram P et al. (2003). J Natl Cancer Inst 95: 1772–1783.

  • Jong K, Marchiori E, Meijer G, van der Vaart A, Ylstra B . (2004). Bioinformatics 20: 3636–3637.

  • Kim SK, Fan YH, Papadimitrakopoulou V, Clayman G, Hittelman WN, Hong WK et al. (1996). Cancer Res 56: 2519–2521.

  • Mao L, Hong WK . (2004). J Natl Cancer Inst 96: 978–980.

  • Mao L, Lee JS, Fan YH, Ro JY, Batsakis JG, Lippman S et al. (1996). Nat Med 2: 682–685.

  • Partridge M, Pateromichelakis S, Phillips E, Emilion GG, A'Hern RP, Langdon JD . (2000). Cancer Res 60: 3893–3898.

  • Pisani P, Bray F, Parkin DM . (2002). Int J Cancer 97: 172–181.

  • Rosin MP, Cheng X, Poh C, Lam WL, Huang Y, Lovas J et al. (2000). Clin Cancer Res 6: 357–362.

  • Snijders AM, Nowak N, Segraves R, Blackwood S, Brown N, Conroy J et al. (2001). Nat Genet 29: 263–264.

  • Tabor MP, Braakhuis BJ, van der Wal JE, van Diest PJ, Leemans CR, Brakenhoff RH et al. (2003). J Pathol 199: 354–360.

  • Tabor MP, Brakenhoff RH, Ruijter-Schippers HJ, Kummer JA, Leemans CR, Braakhuis BJ . (2004). Clin Cancer Res 10: 3607–3613.

  • Tabor MP, Brakenhoff RH, Van Houten VMM, Kummer JA, Snel MHJ, Snijders PJF et al. (2001). Clin Cancer Res 7: 1523–1532.

  • Tsao AS, Kim ES, Hong WK . (2004). CA Cancer J Clin 54: 150–180.

  • Van de Wiel MA, Smeets SJ, Brakenhoff RH, Ylstra B . (2005). Bioinformatics 21: 3193–3194.

  • Van der Riet P, Nawroz H, Hruban RH, Corio R, Tokino K, Koch W et al. (1994). Cancer Res 54: 1156–1158.

  • Van Houten VMM, Snijders PJF, van den Brekel MWM, Kummer JA, Meijer CJLM, Van Leeuwen B et al. (2001). Int J Cancer 93: 232–235.

  • Vogelstein B, Kinzler KW . (2004). Nat Med 10: 789–799.

  • Wreesmann VB, Shi W, Thaler HT, Poluri A, Kraus DH, Pfister D et al. (2004). J Clin Oncol 22: 3965–3972.

  • Zur Hausen H . (2002). Nat Rev Cancer 2: 342–350.

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Acknowledgements

We thank the mapping core and map finishing groups of the Wellcome Trust Sanger Institute for initial BAC clone supply and verification. We are indebted to M Tijssen, PP Eijk, E Hopmans and P van den IJssel for printing slides and technical assistance.

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Authors and Affiliations

  1. Department of Otolaryngology/Head-Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands

    S J Smeets, B J M Braakhuis, S Abbas, C R Leemans & R H Brakenhoff

  2. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands

    P J F Snijders & G A Meijer

  3. Microarray Core Facility, VU University Medical Center, Amsterdam, The Netherlands

    B Ylstra & M A van de Wiel

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  1. S J Smeets
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  2. B J M Braakhuis
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Correspondence to R H Brakenhoff.

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Smeets, S., Braakhuis, B., Abbas, S. et al. Genome-wide DNA copy number alterations in head and neck squamous cell carcinomas with or without oncogene-expressing human papillomavirus. Oncogene 25, 2558–2564 (2006). https://doi.org/10.1038/sj.onc.1209275

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