Molecular Biology Reports

, Volume 40, Issue 7, pp 4161–4171 | Cite as

Heterogeneity of 11q13 region rearrangements in laryngeal squamous cell carcinoma analyzed by microarray platforms and fluorescence in situ hybridization

  • Małgorzata Jarmuz-Szymczak
  • Kinga Pelinska
  • Magdalena Kostrzewska-Poczekaj
  • Ewa Bembnista
  • Maciej Giefing
  • Damian Brauze
  • Marcin Szaumkessel
  • Andrzej Marszalek
  • Joanna Janiszewska
  • Katarzyna Kiwerska
  • Anna Bartochowska
  • Reidar Grenman
  • Witold Szyfter
  • Krzysztof Szyfter
Article
First Online:
Received:
Accepted:

Abstract

We reinvestigated rearrangements occurring in region q13 of chromosome 11 aiming to: (i) describe heterogeneity of the observed structural alterations, (ii) estimate amplicon size and (iii) identify of oncogenes involved in laryngeal cancer progression as potential targets for therapy. The study included 17 cell lines derived from laryngeal cancers and 34 specimens from primary laryngeal tumors. The region 11q13 was analyzed by fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH) and gene expression microarray. Next, quantitative real time PCR was used for chosen genes to confirm results from aCGH and gene expression microarray. The observed pattern of aberrations allows to distinguish three ways, in which gain and amplification involving 11q13 region may occur: formation of a homogeneously staining region; breakpoints in/near 11q13, which lead to the three to sevenfold increase of the copy number of 11q13 region; the presence of additional copies of the whole chromosome 11. The minimal altered region of gain and/or amplification was limited to ~1.8 Mb (chr.11:69,395,184–71,209,568) and comprised mostly 11q13.3 band which contain 12 genes. Five, out of these genes (CCND1, ORAOV1, FADD, PPFIA1, CTTN) had higher expression levels in comparison to healthy controls. Apart from CCND1 gene, which has an established role in pathogenesis of head and neck cancers, CTTN, ORAOV1 and FADD genes appear to be oncogene-candidates in laryngeal cancers, while a function of PPFIA1 requires further studies.

Keywords

Larynx cancer cell lines 11q13 region Amplifications Gains Rearrangements 

Abbreviations

BAC

Bacterial artificial chromosome

CGH array

Comparative genome hybridization

HNSCC

Head neck squamous cell carcinoma

HPV

Human papilloma virus

LSCC

Laryngeal squamous cell carcinoma

MAR

Minimal altered region

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Notes

Acknowledgments

This work was funded by the Polish Ministry of Science and Higher Education Grants, numbers N 403 03 232/1989 and N 401 192 32/4031. We thank Prof. Reiner Siebert (Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel, Christian—Albrechts University 24105 Kiel, Germany) for possibility to perform microarray CGH experiments.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

We declare that all experiments were performed in accordance with the current law of Poland.

Supplementary material

11033_2013_2496_MOESM1_ESM.pdf (100 kb)
Supplementary material 1 (PDF 99 kb)
11033_2013_2496_MOESM2_ESM.pdf (98 kb)
Supplementary material 2 (PDF 97 kb)
11033_2013_2496_MOESM3_ESM.pdf (91 kb)
Supplementary material 3 (PDF 91 kb)

References

  1. 1.
    Ha PK, Califano JA (2003) The molecular biology of mucosal field cancerization of the head and neck. Crit Rev Oral Biol Med 14(5):363–369PubMedCrossRefGoogle Scholar
  2. 2.
    Rautava J, Kuuskoski J, Syrjanen K, Grenman R, Syrjanen S (2012) HPV genotypes and their prognostic significance in head and neck squamous cell carcinomas. J Clin Virol 53(2):116–120. doi: 10.1016/j.jcv.2011.11.005 PubMedCrossRefGoogle Scholar
  3. 3.
    Wang LX, Agulnik M (2008) Promising newer molecular-targeted therapies in head and neck cancer. Drugs 68(12):1609–1619PubMedCrossRefGoogle Scholar
  4. 4.
    Meredith SD, Levine PA, Burns JA, Gaffey MJ, Boyd JC, Weiss LM, Erickson NL, Williams ME (1995) Chromosome 11q13 amplification in head and neck squamous cell carcinoma. Association with poor prognosis. Arch Otolaryngol Head Neck Surg 121(7):790–794PubMedCrossRefGoogle Scholar
  5. 5.
    Mielcarek-Kuchta D, Olofsson J, Golusinski W (2003) p53, Ki67 and cyclin D1 as prognosticators of lymph node metastases in laryngeal carcinoma. Eur Arch Otorhinolaryngol 260(10):549–554. doi: 10.1007/s00405-003-0651-6 PubMedCrossRefGoogle Scholar
  6. 6.
    Xiao-Ping H, Tie-Hua R, Peng L, Qiu-Liang W, Guang-Yu Y, Jing-Hui H, Xiao-Dong S, Xiao-Dong L, Bao-Jiang L, Peng-Yuan Z, Kai L, Zhi-Fan H (2006) Cyclin D1 overexpression in esophageal cancer from southern China and its clinical significance. Cancer Lett 231(1):94–101. doi: 10.1016/j.canlet.2005.01.040 PubMedCrossRefGoogle Scholar
  7. 7.
    Fortin A, Guerry M, Guerry R, Talbot M, Parise O, Schwaab G, Bosq J, Bourhis J, Salvatori P, Janot F, Busson P (1997) Chromosome 11q13 gene amplifications in oral and oropharyngeal carcinomas: no correlation with subclinical lymph node invasion and disease recurrence. Clin Cancer Res 3(9):1609–1614PubMedGoogle Scholar
  8. 8.
    Huang C, Yang L, Li Z, Yang J, Zhao J, Dehui X, Liu L, Wang Q, Song T (2007) Detection of CCND1 amplification using laser capture microdissection coupled with real-time polymerase chain reaction in human esophageal squamous cell carcinoma. Cancer Genet Cytogenet 175(1):19–25. doi: 10.1016/j.cancergencyto.2007.01.003 PubMedCrossRefGoogle Scholar
  9. 9.
    Leemans CR, Braakhuis BJ, Brakenhoff RH (2011) The molecular biology of head and neck cancer. Nat Rev Cancer 11(1):9–22. doi: 10.1038/nrc2982 PubMedCrossRefGoogle Scholar
  10. 10.
    Papadimitrakopoulou VA, Izzo J, Mao L, Keck J, Hamilton D, Shin DM, El-Naggar A, den Hollander P, Liu D, Hittelman WN, Hong WK (2001) Cyclin D1 and p16 alterations in advanced premalignant lesions of the upper aerodigestive tract: role in response to chemoprevention and cancer development. Clin Cancer Res 7(10):3127–3134PubMedGoogle Scholar
  11. 11.
    Izzo JG, Papadimitrakopoulou VA, Liu DD, den Hollander PL, Babenko IM, Keck J, El-Naggar AK, Shin DM, Lee JJ, Hong WK, Hittelman WN (2003) Cyclin D1 genotype, response to biochemoprevention, and progression rate to upper aerodigestive tract cancer. J Natl Cancer Inst 95(3):198–205PubMedCrossRefGoogle Scholar
  12. 12.
    Huang M, Spitz MR, Gu J, Lee JJ, Lin J, Lippman SM, Wu X (2006) Cyclin D1 gene polymorphism as a risk factor for oral premalignant lesions. Carcinogenesis 27(10):2034–2037. doi: 10.1093/carcin/bgl048 PubMedCrossRefGoogle Scholar
  13. 13.
    Rydzanicz M, Golusinski P, Mielcarek-Kuchta D, Golusinski W, Szyfter K (2006) Cyclin D1 gene (CCND1) polymorphism and the risk of squamous cell carcinoma of the larynx. Eur Arch Otorhinolaryngol 263(1):43–48. doi: 10.1007/s00405-005-0957-7 PubMedCrossRefGoogle Scholar
  14. 14.
    Rodrigo JP, Garcia LA, Ramos S, Lazo PS, Suarez C (2000) EMS1 gene amplification correlates with poor prognosis in squamous cell carcinomas of the head and neck. Clin Cancer Res 6(8):3177–3182PubMedGoogle Scholar
  15. 15.
    Gibcus JH, Menkema L, Mastik MF, Hermsen MA, de Bock GH, van Velthuysen ML, Takes RP, Kok K, Alvarez Marcos CA, van der Laan BF, van den Brekel MW, Langendijk JA, Kluin PM, van der Wal JE, Schuuring E (2007) Amplicon mapping and expression profiling identify the Fas-associated death domain gene as a new driver in the 11q13.3 amplicon in laryngeal/pharyngeal cancer. Clin Cancer Res 13(21):6257–6266. doi: 10.1158/1078-0432.CCR-07-1247 PubMedCrossRefGoogle Scholar
  16. 16.
    Jarvinen AK, Autio R, Haapa-Paananen S, Wolf M, Saarela M, Grenman R, Leivo I, Kallioniemi O, Makitie AA, Monni O (2006) Identification of target genes in laryngeal squamous cell carcinoma by high-resolution copy number and gene expression microarray analyses. Oncogene 25(52):6997–7008. doi: 10.1038/sj.onc.1209690 PubMedCrossRefGoogle Scholar
  17. 17.
    Tan KD, Zhu Y, Tan HK, Rajasegaran V, Aggarwal A, Wu J, Wu HY, Hwang J, Lim DT, Soo KC, Tan P (2008) Amplification and overexpression of PPFIA1, a putative 11q13 invasion suppressor gene, in head and neck squamous cell carcinoma. Genes Chromosomes Cancer 47(4):353–362. doi: 10.1002/gcc.20539 PubMedCrossRefGoogle Scholar
  18. 18.
    Jarmuz M, Grenman R, Golusinski W, Szyfter K (2005) Aberrations of 11q13 in laryngeal squamous cell lines and their prognostic significance. Cancer Genet Cytogenet 160(1):82–88. doi: 10.1016/j.cancergencyto.2004.12.006 PubMedCrossRefGoogle Scholar
  19. 19.
    Chomczynski P (1993) A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques 15 (3):532–534, 536–537Google Scholar
  20. 20.
    Giefing M, Martin-Subero JI, Kiwerska K, Jarmuz M, Grenman R, Siebert R, Szyfter K (2008) Characterization of homozygous deletions in laryngeal squamous cell carcinoma cell lines. Cancer Genet Cytogenet 184(1):38–43. doi: 10.1016/j.cancergencyto.2008.03.004 PubMedCrossRefGoogle Scholar
  21. 21.
    Giefing M, Zemke N, Brauze D, Kostrzewska-Poczekaj M, Luczak M, Szaumkessel M, Pelinska K, Kiwerska K, Tonnies H, Grenman R, Figlerowicz M, Siebert R, Szyfter K, Jarmuz M (2011) High resolution ArrayCGH and expression profiling identifies PTPRD and PCDH17/PCH68 as tumor suppressor gene candidates in laryngeal squamous cell carcinoma. Genes Chromosomes Cancer 50(3):154–166. doi: 10.1002/gcc.20840 PubMedCrossRefGoogle Scholar
  22. 22.
    Kostrzewska-Poczekaj M, Giefing M, Jarmuz M, Brauze D, Pelinska K, Grenman R, Bartochowska A, Szyfter W, Szyfter K (2010) Recurrent amplification in the 22q11 region in laryngeal squamous cell carcinoma results in overexpression of the CRKL but not the MAPK1 oncogene. Cancer Biomark 8(1):11–19. doi: 10.3233/DMA-2011-0814 PubMedGoogle Scholar
  23. 23.
    Wessa P (2012) Pearson Correlation (v1.0.6) in Free Statistics Software (v1.1.23-r7), Office for Research Development and Education. http://www.wessa.net/rwasp_correlation.wasp/
  24. 24.
    Shaffer LG, McCaskill C, Han JY, Choo KH, Cutillo DM, Donnenfeld AE, Weiss L, Van Dyke DL (1994) Molecular characterization of de novo secondary trisomy 13. Am J Hum Genet 55(5):968–974PubMedGoogle Scholar
  25. 25.
    Freier K, Sticht C, Hofele C, Flechtenmacher C, Stange D, Puccio L, Toedt G, Radlwimmer B, Lichter P, Joos S (2006) Recurrent coamplification of cytoskeleton-associated genes EMS1 and SHANK2 with CCND1 in oral squamous cell carcinoma. Genes Chromosomes Cancer 45(2):118–125. doi: 10.1002/gcc.20270 PubMedCrossRefGoogle Scholar
  26. 26.
    Tremmel SC, Gotte K, Popp S, Weber S, Hormann K, Bartram CR, Jauch A (2003) Intratumoral genomic heterogeneity in advanced head and neck cancer detected by comparative genomic hybridization. Cancer Genet Cytogenet 144(2):165–174PubMedCrossRefGoogle Scholar
  27. 27.
    Jin C, Jin Y, Gisselsson D, Wennerberg J, Wah TS, Stromback B, Kwong YL, Mertens F (2006) Molecular cytogenetic characterization of the 11q13 amplicon in head and neck squamous cell carcinoma. Cytogenet Genome Res 115(2):99–106. doi: 10.1159/000095228 PubMedCrossRefGoogle Scholar
  28. 28.
    Shuster MI, Han L, Le Beau MM, Davis E, Sawicki M, Lese CM, Park NH, Colicelli J, Gollin SM (2000) A consistent pattern of RIN1 rearrangements in oral squamous cell carcinoma cell lines supports a breakage–fusion–bridge cycle model for 11q13 amplification. Genes Chromosomes Cancer 28(2):153–163PubMedCrossRefGoogle Scholar
  29. 29.
    Gibcus JH, Kok K, Menkema L, Hermsen MA, Mastik M, Kluin PM, van der Wal JE, Schuuring E (2007) High-resolution mapping identifies a commonly amplified 11q13.3 region containing multiple genes flanked by segmental duplications. Hum Genet 121(2):187–201. doi: 10.1007/s00439-006-0299-6 PubMedCrossRefGoogle Scholar
  30. 30.
    Lin M, Smith LT, Smiraglia DJ, Kazhiyur-Mannar R, Lang JC, Schuller DE, Kornacker K, Wenger R, Plass C (2006) DNA copy number gains in head and neck squamous cell carcinoma. Oncogene 25(9):1424–1433. doi: 10.1038/sj.onc.1209166 PubMedCrossRefGoogle Scholar
  31. 31.
    Akervall J, Borg A, Dictor M, Jin C, Jin Y, Tanner M, Isola J, Mertens F, Wennerberg J (2002) Chromosomal translocations involving 11q13 contribute to cyclin D1 overexpression in squamous cell carcinoma of the head and neck. Int J Oncol 20(1):45–52PubMedGoogle Scholar
  32. 32.
    Bellacosa A, Almadori G, Cavallo S, Cadoni G, Galli J, Ferrandina G, Scambia G, Neri G (1996) Cyclin D1 gene amplification in human laryngeal squamous cell carcinomas: prognostic significance and clinical implications. Clin Cancer Res 2(1):175–180PubMedGoogle Scholar
  33. 33.
    Serra-Pages C, Kedersha NL, Fazikas L, Medley Q, Debant A, Streuli M (1995) The LAR transmembrane protein tyrosine phosphatase and a coiled-coil LAR-interacting protein co-localize at focal adhesions. EMBO J 14(12):2827–2838PubMedGoogle Scholar
  34. 34.
    Asperti C, Astro V, Totaro A, Paris S, de Curtis I (2009) Liprin-alpha1 promotes cell spreading on the extracellular matrix by affecting the distribution of activated integrins. J Cell Sci 122(Pt 18):3225–3232. doi: 10.1242/jcs.054155 PubMedCrossRefGoogle Scholar
  35. 35.
    Shen JC, Unoki M, Ythier D, Duperray A, Varticovski L, Kumamoto K, Pedeux R, Harris CC (2007) Inhibitor of growth 4 suppresses cell spreading and cell migration by interacting with a novel binding partner, liprin alpha1. Cancer Res 67(6):2552–2558. doi: 10.1158/0008-5472.CAN-06-3870 PubMedCrossRefGoogle Scholar
  36. 36.
    Dancau AM, Wuth L, Waschow M, Holst F, Krohn A, Choschzick M, Terracciano L, Politis S, Kurtz S, Lebeau A, Friedrichs K, Wencke K, Monni O, Simon R (2010) PPFIA1 and CCND1 are frequently coamplified in breast cancer. Genes Chromosomes Cancer 49(1):1–8. doi: 10.1002/gcc.20713 PubMedCrossRefGoogle Scholar
  37. 37.
    Huang X, Gollin SM, Raja S, Godfrey TE (2002) High-resolution mapping of the 11q13 amplicon and identification of a gene, TAOS1, that is amplified and overexpressed in oral cancer cells. Proc Natl Acad Sci USA 99(17):11369–11374. doi: 10.1073/pnas.172285799 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Małgorzata Jarmuz-Szymczak
    • 1
    • 2
  • Kinga Pelinska
    • 1
  • Magdalena Kostrzewska-Poczekaj
    • 1
  • Ewa Bembnista
    • 2
  • Maciej Giefing
    • 1
  • Damian Brauze
    • 1
  • Marcin Szaumkessel
    • 1
  • Andrzej Marszalek
    • 3
    • 4
  • Joanna Janiszewska
    • 1
  • Katarzyna Kiwerska
    • 1
  • Anna Bartochowska
    • 5
  • Reidar Grenman
    • 6
    • 7
  • Witold Szyfter
    • 5
  • Krzysztof Szyfter
    • 1
    • 5
  1. 1.Institute of Human Genetics, Polish Academy of SciencesPoznanPoland
  2. 2.Department of HematologyUniversity of Medical SciencesPoznanPoland
  3. 3.Department of Clinical PathomorphologyCollegium Medicum, Nicolaus Copernicus UniversityBydgoszczPoland
  4. 4.Department of Oncologic PathologyGreater Poland Cancer CentrePoznanPoland
  5. 5.Department of OtolaryngologyUniversity of Medical SciencesPoznanPoland
  6. 6.Department of Otorhinolaryngology—Head and Neck SurgeryTurku University Hospital and University of TurkuTurkuFinland
  7. 7.Department of Medical BiochemistryTurku University Hospital and University of TurkuTurkuFinland

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