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

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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.

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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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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.

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Authors and Affiliations

  1. Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479, Poznan, Poland

    Małgorzata Jarmuz-Szymczak, Kinga Pelinska, Magdalena Kostrzewska-Poczekaj, Maciej Giefing, Damian Brauze, Marcin Szaumkessel, Joanna Janiszewska, Katarzyna Kiwerska & Krzysztof Szyfter

  2. Department of Hematology, University of Medical Sciences, Szamarzewskiego 82/84, 60-569, Poznan, Poland

    Małgorzata Jarmuz-Szymczak & Ewa Bembnista

  3. Department of Clinical Pathomorphology, Collegium Medicum, Nicolaus Copernicus University, Skłodowskiej-Curie 9, 85-094, Bydgoszcz, Poland

    Andrzej Marszalek

  4. Department of Oncologic Pathology, Greater Poland Cancer Centre, Garbary 15, 61-688, Poznan, Poland

    Andrzej Marszalek

  5. Department of Otolaryngology, University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznan, Poland

    Anna Bartochowska, Witold Szyfter & Krzysztof Szyfter

  6. Department of Otorhinolaryngology—Head and Neck Surgery, Turku University Hospital and University of Turku, PO Box 52, FI-20521, Turku, Finland

    Reidar Grenman

  7. Department of Medical Biochemistry, Turku University Hospital and University of Turku, PO Box 52, FI-20521, Turku, Finland

    Reidar Grenman

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  1. Małgorzata Jarmuz-Szymczak
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  2. Kinga Pelinska
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Correspondence to Małgorzata Jarmuz-Szymczak.

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Jarmuz-Szymczak, M., Pelinska, K., Kostrzewska-Poczekaj, M. et al. Heterogeneity of 11q13 region rearrangements in laryngeal squamous cell carcinoma analyzed by microarray platforms and fluorescence in situ hybridization. Mol Biol Rep 40, 4161–4171 (2013). https://doi.org/10.1007/s11033-013-2496-4

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  • DOI: https://doi.org/10.1007/s11033-013-2496-4

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